The KCNJ11 NM_000525.4:c.602G>A (NP_000516.3:p.(Arg201His)) missense variant has not previously been reported in somatic cancers (COSMIC). Experimental evidence: Independent beta-cell, mammalian-cell, and oocyte assays consistently showed R201H reduced ATP sensitivity, surface expression, electrical activation, and insulin secretion. Based on available guidelines, this variant is considered to be Pathogenic.
Five-step scale from benign to pathogenic. This variant is pathogenic. Select a step to read what it means.
Pathogenic.A pathogenic classification under the recorded framework.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.KCNJ11 encodes an inward-rectifier potassium channel that helps regulate electrical activity and insulin release in cells. Changes in this gene are associated with neonatal diabetes, type 2 diabetes, and familial persistent hyperinsulinemic hypoglycemia of infancy. KCNJ11 has no established cancer-related role.
The recorded framework is Generic ACMG/AMP 2015 with ClinGen SVI recommendations. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
The applied criteria and their strengths are shown as assessed under the stated framework.
Met: the exact p.Arg201His change was reported in 11 families and 14 patients and independently characterized in functional studies.
Met at moderate strength: independent beta-cell, mammalian-cell, and oocyte assays consistently showed R201H reduced ATP sensitivity, surface expression, electrical activation, and insulin secretion.
Met: one R201H carrier among 11 probands versus 0/100 controls gave continuity-corrected OR 28.7 (95% CI 1.10-750.38), exceeding OR >5 with CI excluding 1.
Met: Arg201 is explicitly identified as a neonatal-diabetes hotspot, and R201H is absent from gnomAD v2.1 and v4.1.
Met at supporting strength: AF is 0 in gnomAD v2.1 (0/248,530) and v4.1 (0/1,612,208), below the <=0.0001 PM2 threshold.
Met: different missense substitutions at Arg201, including R201C and R201L, were reported in KCNJ11 neonatal diabetes.
Met at supporting strength: p.Arg201His co-segregated with permanent neonatal diabetes in the affected proband and her affected mother.
Met, strong: missense REVEL 0.982 exceeds the supplied PP3 strong threshold of 0.932.
No benign criterion marked as applied in the recorded assessment.
Pathogenic: PS1 and PS4 strong, PS3/PM1/PM5 moderate, PP1/PM2 supporting, and PP3 strong satisfy generic ACMG/AMP rules.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 0 / 1,612,208 alleles. Recorded AF 0. Recorded homozygote count 0.
This variant is present in gnomAD v2.1 (AF= 0; MAF= 0.00000%, 0/248530 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/16168 alleles, homozygotes = 0).
Not available in gnomAD-Canada v1.0.
Recorded REVEL score: 0.982. Refer to the recorded PP3/BP4 rationale for interpretation.
10 Pathogenic. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
No standalone functional evidence summary is recorded in evidence_summary.functional.
This variant has not previously been reported in somatic cancers (COSMIC).
This variant does not lie in a statistically significant hotspot.
ACMG/AMP criteria under Generic ACMG/AMP 2015 with ClinGen SVI recommendations, with the data and sources behind each one.
28 criteria with recorded statuses: 8 met · 10 not met · 6 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
The codon/residue evidence supports PS1, PM1, and PM5 for KCNJ11 p.Arg201His; PP2 remains unassessed because its gene-level benign-missense requirement is not quantified, and BP1 is not met.
Segregation/de novo evidence supports PP1 at supporting strength from one affected mother-proband pair; PS2 is not met because the documented case is maternally inherited, while PM6 and BS4 lack qualifying evidence.
PS4 is met from a sparse case-control comparison: R201H occurred in 1/11 affected probands and 0/100 nondiabetic Caucasian controls; continuity-corrected OR 28.71, 95% CI 1.10-750.38.
PP4 is not met because neonatal diabetes has multiple genetic etiologies and is not highly specific for KCNJ11.
PP5 and BP6 are not triggered because the exact variant has no ClinVar expert-panel classification; available assertions are clinical-laboratory Pathogenic submissions.
BP5 is not assessed because no case-level alternate molecular basis for the disease was documented.
Population evidence supports PM2 at supporting strength because the variant is absent from gnomAD v2.1 and v4.1, while BA1, BS1, and BS2 are not met.
The zero observed frequency does not provide benign population evidence; it is concordant with the documented early-onset neonatal-diabetes association and pathogenic ClinVar consensus.
No criteria match.
The queried variant is NP_000516.3:p.(Arg201His) (R201H). Multiple independent publications explicitly report the same amino-acid substitution in KCNJ11 in patients with permanent or transient neonatal diabetes, including functional studies of R201H. PMID:15448106 reports the R201H substitution in family AA with permanent neonatal diabetes; PMID:16609879 reports R201H in 11 families and 14 patients; PMID:17065345 and PMID:15718250 experimentally characterize the exact R201H variant. These reports establish the same amino-acid change as disease-causing regardless of nucleotide change.
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change. ... Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
PS3 is met at moderate strength. Three independent peer-reviewed functional studies directly evaluated KCNJ11 p.Arg201His (c.602G>A; R201H) using biologically relevant KATP-channel systems. Lin et al. (PMID:16731837) used mammalian COSm6, HEK293, and N2a cells with wild-type controls, electrophysiology, Western blotting, and surface-expression assays, finding reduced ATP sensitivity and approximately 80% reduced surface expression for R201H. Männikkö et al. (PMID:17065345) used inducible stable INS-1 beta-cell expression with wild-type controls and patch-clamp, membrane-potential, and insulin-secretion assays; R201H increased the ATP IC50 from approximately 20 micromol/l to approximately 2 mmol/l, prevented metabolically induced channel closure and electrical activation, and abolished methyl-succinate-stimulated insulin secretion. Kassem et al. (PMID:15718250) independently tested R201H in Xenopus oocytes expressing Kir6.2/SUR1 and found markedly reduced ATP sensitivity and increased channel current. These findings are concordant, mechanistically linked to KCNJ11/Kir6.2 control of beta-cell electrical activity and insulin secretion, and include appropriate wild-type or comparator controls. Moderate rather than strong strength is assigned because the available studies are research assays and do not demonstrate validation, reproducibility, and robustness in a clinical diagnostic laboratory setting as emphasized by the governing definition.
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product. Note: Functional studies that have been validated and shown to be reproducible and robust in a clinical diagnostic laboratory setting are considered the most well-established.
PMID:15448106 reports one R201H carrier among 11 probands with permanent neonatal diabetes and no R201H among 100 nondiabetic Caucasian controls. This is a case-control comparison even though the paper does not print an odds ratio. Using a Haldane-Anscombe 0.5 continuity correction for the zero control cell, OR = (1.5 x 100.5)/(10.5 x 0.5) = 28.71 and the Wald 95% CI is 1.10-750.38; therefore OR > 5.0 and the confidence interval excludes 1.0. PMID:16609879 independently reports R201H in 11 families and 14 patients with permanent diabetes. The sparse counts and wide confidence interval warrant human review, but the generic PS4 threshold is met.
The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls. ... Note 1: Relative risk (RR) or odds ratio (OR), as obtained from case-control studies, is >5.0 and the confidence interval around the estimate of RR or OR does not include 1.0.
The variant changes residue Arg201, and PMID:27681997 explicitly states that arginine 201 is a hotspot of neonatal-diabetes mutations. The same source documents R201C, R201H, and R201L in KCNJ11 neonatal diabetes, while the queried R201H allele is absent from gnomAD v2.1 (0/248,530 alleles) and gnomAD v4.1 (0/1,612,208 alleles). This supports a disease-associated mutational hotspot without observed population variation for the queried missense allele; no VCEP domain table applies because no VCEP covers KCNJ11.
Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.
PM2 is met at supporting strength. NM_000525.4:c.602G>A (p.Arg201His) is absent from the default all-comers population datasets: gnomAD v2.1 exomes show 0/248,530 alleles and gnomAD v4.1 shows 0/1,612,208 alleles, with 0 homozygotes in both. No governing VCEP specifies a non-cancer or exome-only subset for this generic interpretation, so the all-comers gnomAD v2.1 and v4.1 entries are the applicable defaults. The supplied generic PM2 threshold is <=0.0001, and the observed AF is 0.
Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
The queried variant is p.Arg201His. PMID:27681997 reports other missense substitutions at the same residue, including R201C and R201L, and documents R201C in patients with KCNJ11 neonatal diabetes and iDEND syndrome; it also states that R201C and R201L had been previously reported. These are different missense changes at Arg201 associated with the same disease spectrum, satisfying the classic same-residue PM5 pattern.
Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before. ... Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
PP1 is met at supporting strength. In family AA, the exact KCNJ11 p.Arg201His variant was identified in the affected proband and her affected mother, providing co-segregation with permanent neonatal diabetes in multiple affected family members. Only one affected parent-proband pair is documented, so no stronger use is assigned.
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease. ... May be used as stronger evidence with increasing segregation data.
The variant is a missense substitution, NM_000525.4:c.602G>A (p.Arg201His), so the generic missense path requires REVEL and excludes SpliceAI from PP3/BP4 assessment. REVEL is 0.982, meeting the supplied generic ClinGen SVI strong PP3 threshold of >=0.932 (Pejaver et al. 2022, PMID:36413997). BayesDel is not used because no generic ACMG-strength calibration is established.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.).
PS2 is not met. The directly extracted family-level evidence for p.Arg201His reports the variant in the proband and her affected mother, demonstrating inheritance rather than de novo occurrence. No evidence establishes a de novo event with both maternity and paternity confirmed in a patient without family history.
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
The reported phenotype is neonatal diabetes, including permanent or transient neonatal diabetes, but this phenotype is not highly specific for a single genetic etiology. The literature and the Japanese cohort include both KCNJ11- and ABCC8-associated neonatal diabetes, so generic PP4 is not satisfied.
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
The exact variant has Pathogenic clinical-laboratory and literature-linked assertions in ClinVar, but the ClinVar record reports zero expert-panel submissions. Under the required generic rule, ordinary laboratory submissions, aggregate ClinVar labels, and non-expert assertions do not trigger PP5.
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
BA1 is not met. The variant has observed AF 0.00000% in gnomAD v2.1 exomes (0/248,530 alleles) and gnomAD v4.1 all-comers (0/1,612,208 alleles), with 0 homozygotes. The reported grpmax FAF is null because no alternate alleles were observed; no popmax point estimate supports BA1. These observed frequencies are far below the generic stand-alone threshold of >=0.05. The variant has a pathogenic ClinVar consensus and a well-established early-onset neonatal-diabetes association, so there is no population-frequency basis to override that evidence with BA1.
Allele frequency is above 5% in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
BS1 is not met. The variant's observed AF is 0.00000% in gnomAD v2.1 exomes (0/248,530 alleles) and gnomAD v4.1 all-comers (0/1,612,208 alleles), with no observed alternate alleles in any reported ancestry and no homozygotes. The reported grpmax FAF is null because the alternate allele count is zero; there is no elevated filtering frequency to compare with the disorder's maximum credible allele frequency. KCNJ11 R201H is associated with neonatal diabetes presenting in infancy, so the supplied 1% generic BS1 default is not approached.
Allele frequency is greater than expected for the disorder.
BS2 is not met. This criterion requires observation of the variant in a healthy adult in the relevant fully penetrant early-onset inheritance context. gnomAD v2.1 and v4.1 show no alternate alleles and no homozygotes, so they provide no healthy adult carrier observation. Published reports instead describe heterozygous R201H in affected individuals with neonatal diabetes diagnosed in infancy, including a family with permanent neonatal diabetes; these observations do not satisfy BS2.
Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
BS3 is not met. The available variant-specific functional studies do not show no damaging effect; instead, independent assays consistently demonstrate abnormal KATP-channel function and expression for R201H, including markedly reduced ATP sensitivity, increased channel activity, impaired surface expression, failure of metabolic electrical activation, and impaired insulin secretion. No well-established benign functional or splicing result for this variant was identified.
Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
BP1 does not apply because the available KCNJ11 disease literature describes activating missense variation as a common mechanism of neonatal diabetes. PMID:16609879 reports 14 different heterozygous missense mutations in affected patients, and PMID:27681997 describes multiple KCNJ11 missense mutations causing neonatal diabetes; the supplied evidence does not show that disease in this gene is primarily caused by truncating variants.
Missense variant in a gene for which primarily truncating variants are known to cause disease.
The variant is a missense substitution, so the applicable generic BP4 path is REVEL only; SpliceAI is not evidence for BP4 in this situation. REVEL is 0.982, which exceeds all supplied BP4 benign thresholds (supporting <=0.29, moderate <=0.183, strong <=0.016), so BP4 is not met. BayesDel is not used because no generic ACMG-strength calibration is established.
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc)
No exact-variant ClinVar expert-panel classification of Benign or Likely benign is present. The record instead contains Pathogenic clinical-laboratory assertions and no expert-panel submission, so BP6 is not triggered.
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
PM3 cannot be assessed because the available variant-specific evidence reports heterozygous KCNJ11 p.Arg201His in an affected proband and her affected mother but does not document a second pathogenic variant, parental testing establishing trans phase, or offspring testing. The reported phenotype is neonatal diabetes, and no evidence establishes that this variant is present in trans with a pathogenic allele in a recessive KCNJ11 disorder.
PM3: For recessive disorders, detected in trans with a pathogenic variant Note: This requires testing of parents (or offspring) to determine phase.
PM6 is not assessed. The available primary family report documents maternal transmission in family AA, while no qualifying report with an assumed de novo occurrence and absent maternity and paternity confirmation provides sufficient case-level details for this criterion.
Assumed de novo, but without confirmation of paternity and maternity.
The literature supports missense variants as a common disease mechanism in KCNJ11: activating KCNJ11 missense mutations cause neonatal diabetes, and PMID:16609879 reports 14 different heterozygous missense mutations in its cohort. However, the supplied evidence does not provide a gene-level rate or defined threshold demonstrating a low rate of benign missense variation, and the absence of this single allele from gnomAD cannot establish that gene-level requirement.
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
BS4 is not assessed. The available evidence documents an affected mother carrying the variant with the proband, but does not provide an affected relative who lacks the variant; therefore lack of segregation cannot be established.
Lack of segregation in affected members of a family.
BP2 cannot be assessed because the available evidence does not document the variant in trans with a pathogenic variant in an applicable fully penetrant dominant disorder, nor in cis with a pathogenic variant in any inheritance pattern. The available family observation reports the variant alone as heterozygous in an affected proband and her affected mother and provides no cis/trans result for another pathogenic allele.
BP2: Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
The reviewed evidence documents KCNJ11 R201H in patients with neonatal diabetes but does not establish that an affected case had an alternate molecular basis for the disease. No qualifying BP5 case-level alternate diagnosis is available in the supplied evidence.
Variant found in a case with an alternate molecular basis for disease.
PVS1 (ClinGen SVI PVS1 recommendations, PMC6185798, pvs1_generic_framework) applies only to null variant classes — nonsense, frameshift, canonical ±1/2 splice-consensus, translation-initiation-codon loss, and stop-loss variants — each expected to trigger nonsense-mediated decay or otherwise abolish normal protein function. NM_000525.4:c.602G>A in KCNJ11 is a missense substitution predicted to produce NP_000516.3:p.(Arg201His). As a result, no null-variant mechanism (nonsense-mediated decay, truncation, or canonical splice disruption) is triggered by this variant class, so PVS1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PVS1 for KCNJ11, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_null_variant_class
PM4 (Richards et al. 2015, PMID:25741868) applies to protein length changes: in-frame insertions/deletions in a non-repetitive region, or stop-loss variants that extend the protein past the reference stop codon. NM_000525.4:c.602G>A in KCNJ11 is a missense substitution predicted to produce NP_000516.3:p.(Arg201His). As a result, no change in protein length occurs, so there is nothing for this criterion to evaluate, so PM4's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM4 for KCNJ11, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_stop_loss_or_nonrepeat_indel
BP3 (Richards et al. 2015, PMID:25741868) applies to in-frame insertions/deletions located in a repetitive region without a known function. NM_000525.4:c.602G>A in KCNJ11 is a missense substitution predicted to produce NP_000516.3:p.(Arg201His). As a result, the variant does not alter protein length within a repeat region, so there is nothing for this criterion to evaluate, so BP3's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP3 for KCNJ11, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_repeat_region_indel
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_000525.4:c.602G>A in KCNJ11 is a missense substitution predicted to produce NP_000516.3:p.(Arg201His). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for KCNJ11, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
Every interpreted variant in KCNJ11, mapped onto the exon structure of NM_000525.4. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
This variant is present in gnomAD v4.1 (AF= 0; MAF= 0.00000%, 0/1612208 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/75044 alleles, homozygotes = 0).
This variant is present in gnomAD v2.1 (AF= 0; MAF= 0.00000%, 0/248530 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/16168 alleles, homozygotes = 0).
Not available in gnomAD-Canada v1.0.
The variant is a missense substitution, NM_000525.4:c.602G>A (p.Arg201His), so the generic missense path requires REVEL and excludes SpliceAI from PP3/BP4 assessment. REVEL is 0.982, meeting the supplied generic ClinGen SVI strong PP3 threshold of >=0.932 (Pejaver et al. 2022, PMID:36413997). BayesDel is not used because no generic ACMG-strength calibration is established.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.).
The variant is a missense substitution, so the applicable generic BP4 path is REVEL only; SpliceAI is not evidence for BP4 in this situation. REVEL is 0.982, which exceeds all supplied BP4 benign thresholds (supporting <=0.29, moderate <=0.183, strong <=0.016), so BP4 is not met. BayesDel is not used because no generic ACMG-strength calibration is established.
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc)
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_000525.4:c.602G>A in KCNJ11 is a missense substitution predicted to produce NP_000516.3:p.(Arg201His). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for KCNJ11, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.982. BayesDel score = 0.591382.
9 paper records listed. 6 cited in the classification.
The mutations CGT to CAT and GTG to ATG, corresponding to the previously described PND-associated amino acid substitutions Val59Met (V59M) and Arg201His (R201H), respectively, were identified in families N546 (V59M), IS3 (V59M), IS4 (V59M), and AA (R201H).
Location Results, paragraph 2; Table 1, family AA
Context KCNJ11 sequencing in 11 probands with GCK-negative permanent neonatal diabetes; family AA underwent tolbutamide and glibenclamide treatment evaluation.
The R201H mutation associated with PNDM results in a decreased sensitivity to ATP
Location Introduction; Functional analysis; Figure 3; Table 2
Context Xenopus laevis oocytes expressing human Kir6.2/KCNJ11 with SUR1; whole-cell voltage-clamp and inside-out patch recordings.
The most common mutation, R201H, was associated with isolated diabetes in all of the 14 patients
Location Results, genotype–phenotype relationship paragraph; Table 2
Context KCNJ11 sequencing in 239 unrelated patients with permanent diabetes diagnosed before age 2 years, with clinical and neurological assessment of mutation-positive patients.
PNDM mutations, including Q52R, V59G, V59M, R201C, R201H, and I296L, not only reduce channel ATP sensitivity but also impair channel expression at the cell surface to varying degrees.
Location Abstract; Results, ‘Effects of PNDM mutations on KATP channel expression’; Figure 1
Context Wild-type and mutant Kir6.2/SUR1 expressed in COSm6, HEK293, and N2a mammalian cells; Western blotting, chemiluminescence surface-expression assays, and patch-clamp electrophysiology with wild-type controls.
Induction of Kir6.2-R201H expression strongly reduced KATP channel ATP sensitivity (the half-maximal inhibitory concentration increased from ~20 micromol/l to ~2 mmol/l), and the metabolic substrate methyl succinate failed to close KATP channels or stimulate electrical activity and insulin secretion.
Location Abstract; Results, ATP sensitivity, whole-cell KATP currents, and insulin secretion measurements; Table 1 and Figures 2–6
Context Stable tetracycline-inducible expression of wild-type or R201H Kir6.2 in INS-1 beta cells with patch-clamp, membrane-potential, and insulin-secretion assays.
Arginine at position 201 is a hot spot of NDM mutations. Although R201C, R201H, and R201L mutations have been reported, R201G (patient 6) has not been reported.
Location Results, section 3.1; Table 2, patients 5, 6, 7, and 12; Discussion
Context Japanese cohort of 25 patients with KATP-channel neonatal diabetes identified by sequencing all KCNJ11 and ABCC8 exons and exon-intron boundaries; 16 patients had KCNJ11 mutations.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
This variant is present in gnomAD v4.1 (AF= 0; MAF= 0.00000%, 0/1612208 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/75044 alleles, homozygotes = 0).
This variant is present in gnomAD v2.1 (AF= 0; MAF= 0.00000%, 0/248530 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/16168 alleles, homozygotes = 0).
Not available in gnomAD-Canada v1.0.
This variant has been reported in ClinVar as Pathogenic (10 clinical laboratories). (ClinVarID = 8666)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.982. BayesDel score = 0.591382.
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
This variant does not lie in a statistically significant hotspot.