The RYR1 NM_000540.3:c.1840C>T (NP_000531.2:p.(Arg614Cys)) missense variant has previously been reported in somatic cancers (COSMIC; COSV100616513, n = 1 time). Based on available guidelines, this variant is considered to be a Variant of Uncertain Significance (VUS). This variant is considered to be drug response by the VCEP (ClinPGx; ClinVar ID 12964).
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.RYR1 encodes a calcium-release channel in skeletal muscle that helps connect the sarcoplasmic reticulum with the transverse tubules and regulate muscle contraction. Changes in RYR1 are associated with malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia; it has no established cancer role.
The recorded framework is ClinGen RYR1 VCEP v2.0. 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 at moderate strength: REVEL 0.927 exceeds the VCEP's >0.85 threshold for deleterious computational evidence.
Not applicable: the RYR1 VCEP states that PP5 is not for use under the ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation.
No benign criterion marked as applied in the recorded assessment.
VUS: PP3 (moderate) plus PP5 (supporting) do not satisfy any ACMG/AMP 2015 pathogenic, likely pathogenic, benign, or likely benign combination rule.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 118 / 1,614,054 alleles. Recorded AF 7.31078e-05. Recorded homozygote count 0.
This variant is present in gnomAD v2.1 (AF= 0.000106059; MAF= 0.01061%, 30/282862 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000193519; MAF= 0.01935%, 25/129186 alleles, homozygotes = 0); grpmax FAF= 0.00021229.
This variant is present in gnomAD-Canada v1.0 (AF= 0.0001086484137331595, 2/18408 alleles, homozygotes = 0).
Recorded REVEL score: 0.927. Refer to the recorded PP3/BP4 rationale for interpretation.
27 Pathogenic · 1 pathogenic. ClinVar API review status: reviewed by expert panel.
No standalone functional evidence summary is recorded in evidence_summary.functional.
This variant has previously been reported in somatic cancers (COSMIC; COSV100616513, n = 1 times).
This variant does not lie in a statistically significant hotspot.
ACMG/AMP criteria under ClinGen RYR1 VCEP v2.0, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 6 not met · 8 not assessed · 12 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Among the requested codon, residue, and domain criteria, none provides usable positive or negative evidence for this RYR1 p.Arg614Cys variant: PS1 lacks a distinct same-amino-acid nucleotide change, PM1 excludes residue 614, PM5 lacks an alternate residue-614 missense variant, and PP2/BP1 are VCEP-not-applicable.
PS2 and PM6 are not assessed because no qualifying proven or assumed de novo case has sufficient documented parental-origin evidence.
PP1 is not assessed because the available extracted reports do not provide an exact count of qualifying disease-cosegregating meioses.
BS4 is not applicable under the RYR1 VCEP specification.
Only PS4, PP4, PP5, BP5, and BP6 were adjudicated.
PS4 remains not assessed because the available variant-specific evidence does not establish the VCEP-required case-point total or a qualifying odds ratio with 95% confidence interval; PP4, PP5, BP5, and BP6 are explicitly not applicable in the RYR1 VCEP specification.
Population evidence is limited to the four requested criteria: BA1 and BS1 are not met because the VCEP popmax thresholds are not exceeded; BS2 is not assessed because the required healthy-adult negative IVCT/CHCT observation is unavailable; PM2 is not applicable under the VCEP.
All-comers gnomAD totals and population maxima were used because the VCEP text does not specify a non-cancer or exome-only population source for these criteria.
No criteria match.
The variant is a missense SNV, so the VCEP's PP3 missense computational path applies. That path names REVEL and specifies a score greater than 0.85; the case-specific REVEL score is 0.927, which meets the VCEP threshold. No splice predictor or other computational predictor is counted for PP3 because the governing rule names REVEL for this path.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product ... * Use REVEL score of >0.85
Expert panel ClinGen Malignant Hyperthermia Susceptibility Variant Curation Expert Panel, ClinGen classified as Pathogenic.
This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.
The variant is RYR1 p.Arg614Cys (c.1840C>T). The available evidence establishes this exact nucleotide change as pathogenic, but does not identify a different nucleotide change producing the same Arg614Cys amino-acid substitution. Therefore the VCEP's same-amino-acid PS1 requirement is not met.
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change * Previously established pathogenic variant must reach a classification of pathogenic without PS1
RYR1 residue 614 is outside every region specified by the VCEP: residues 1-552, 2,101-2,458, and 4,631-4,991. The VCEP materials contain no RYR1 domain-table entry and the VCEP rule does not name an independent hotspot source route. PM1 is therefore not met.
Located in a mutational hot spot and/or critical and well established functional domain. * Residues 1-552 (N-terminal region) and 2,101-2,458 (central region) * PM1 should not be applied at a moderate weight with PS1/PM5, see PM1_Supporting. ... Located in a mutational hot spot and/or critical and well established functional domain. * Residues 1-552 (N-terminal region) and 2,101-2,458 (central region), if PS1/PM5 applicable then PM1 should be used at supporting * Residues 4,631-4,991 (C-terminal region).
The variant is a missense change at residue 614, but the collected same-residue comparator review found zero same-residue candidates and no qualifying pathogenic or likely pathogenic alternate missense variant. The VCEP PM5 requirement is therefore not met.
Missense change at an amino acid residue where a different missense varaint previously determined to be pathogenic * Previously established pathogenic variant must reach a classification of pathogenicity without PM5 * Grantham score for alternate pathogenic variant must be less than for variant being assessed ... Missense change at an amino acid residue where a different missense variant previously determined to be pathogenic. * Previously established likely pathogenic variant can be considered supporting evidence, must reach a classification of likely pathogenic without PM5. * Grantham score for alternate likely pathogenic variant must be less than for variant being assessed.
The RYR1 VCEP specifies BA1 when popmax allele frequency is >0.0038 (0.38%). The highest available all-comers gnomAD population frequency is the gnomAD v2.1 grpmax FAF of 0.00021229 (0.021229%), and gnomAD v4.1 grpmax FAF is 0.00007408 (0.007408%); both are below 0.0038. The VCEP does not specify a non-cancer or exome-only source for BA1, so the all-comers values are used.
Popmax allele frequency >0.0038 (0.38%)
The RYR1 VCEP specifies BS1 at strong strength when popmax allele frequency is >0.0008 (0.08%). The highest available all-comers gnomAD population frequency is the gnomAD v2.1 grpmax FAF of 0.00021229 (0.021229%), with gnomAD v4.1 grpmax FAF of 0.00007408 (0.007408%); neither exceeds 0.0008. The VCEP does not specify a non-cancer or exome-only source for BS1, so the all-comers values are used.
Popmax allele frequency >0.0008 (0.08%)
The variant is a missense SNV and therefore is within the VCEP's BP4 computational scope. The governing rule names REVEL and requires a score below 0.5 for no computational impact. The case-specific REVEL score is 0.927, so the BP4 threshold is not met. SpliceAI is not counted because the VCEP BP4 rule names REVEL, not SpliceAI, for this situation.
Computational evidence suggest no impact on gene or gene product, REVEL score of <0.5
No qualifying proven or assumed de novo case is documented for RYR1 c.1840C>T. The reviewed family evidence describes inherited R614C transmission, including R614C in a mother and in her children, rather than a proband with documented parental-origin testing. The VCEP point-based PS2 rule therefore cannot be evaluated.
The variant-specific functional evidence is directionally damaging but does not satisfy a defined VCEP calibration path. Yang et al. (PMID:12732639) expressed the corresponding R614C RyR1 construct in RyR-null dyspedic skeletal myotubes and reported significantly increased sensitivity to caffeine and 4-chloro-m-cresol versus WT, with calcium imaging, WT comparison, and replicate experiments. However, this is not the VCEP's specified HEK293 assay, and the available evidence does not document three or more independent ex vivo studies, a knock-in mouse with the required paired findings, or the VCEP-required HEK293 controls and n≥3. The Swiss IVCT study (PMID:11668625) reports stronger contracture effects for R614C but does not establish one of the VCEP's listed PS3 calibration paths. Therefore PS3 is not assessed rather than assigned a strength.
Well-established functional studies supportive of a damaging effect on protein function * Increased sensitivity to RYR1 agonist in HEK293 in vitro assay, Ca2+ release significantly increased compared to WT, controls to include known pathogenic and benign variants, n≥3. * Three or more independent ex vivo studies all showing release of Ca2+ in response to RYR1 agonist * Knock-in mouse showing MH reaction in response to RYR1 agonist OR increased sensitivity to RYR1 agonists in ex vivo tissue/cells (but not both, which would be PS3_strong)...Well-established functional studies supportive of a damaging effect on protein function * Two independent ex vivo studies all showing release of Ca2+ in response to RYR1 agonist
The RYR1 VCEP PS4 rule requires either a defined number of MH case points with popmax gnomAD ≤0.00006, or an odds ratio threshold when popmax gnomAD >0.00006. The reviewed variant-specific literature includes a Swiss cohort reporting R614C in 3 of 48 unrelated MH families and 65 MHS plus 9 MHE mutation-positive patients, but it does not provide the VCEP-defined MH case-point total or a case/control allele-count table sufficient to calculate the required odds ratio and 95% CI. The gnomAD v4.1 popmax FAF is 0.00007408, so the >0.00006 odds-ratio route is applicable: 0.00007408 > 0.00006? yes; however, no qualifying OR and 95% CI can be established from the available evidence. The literature-pass PS4 leads were checked against their available abstract records, and the fetched full-text extracts were checked where available; they report family occurrence, segregation, functional data, or general RYR1 findings rather than a qualifying case-control comparison for this variant.
The prevalence of the variant in affected individuals significantly increased compared with the prevalence in controls. * ≥7 MH case points. Probands with a personal or family history of an MH event are awarded 0.5 points, probands with a personal or family history of a positive (MHS) IVCT/CHCT are awarded an additional 0.5 points. Probands with multiple variants in RYR1 classified as VUS, likely pathogenic or pathogenic are not considered. Popmax in gnomAD ≤0.00006. * For variants with popmax MAF gnomAD >0.00006, an odds ratio of ≥18.7 when comparing MH case points to allele count in gnomAD can qualify. Popmax in gnomAD must be <0.0038. ... The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls. * 2-6 MH case points. Probands with a personal or family history of an MH event are awarded 0.5 points, probands with a personal or family history of a positive (MHS) IVCT/CHCT are awarded an additional 0.5 points. Probands with multiple variants in RYR1 classified as VUS, likely pathogenic or pathogenic are not considered. Popmax in gnomAD ≤0.00006. * For variants with popmax MAF in gnomAD >0.00006, an odds ratio of ≥4.33 when comparing MH case points to allele count in gnomAD can qualify. Popmax in gnomAD must be <0.0038. ... The prevalence of the variant in affected individuals is significantly increased compared withthe prevalence in controls. * 1 MH case point. Probands with a personal or family history of an MH event are awarded 0.5 points, probands with a personal or family history of a positive (MHS) IVCT/CHCT are awarded an additional 0.5 points. Probands with multiple variants in RYR1 classified as VUS, likely pathogenic or pathogenic are not considered. Popmax in gnomAD ≤0.00006. For variants with popmax MAF in gnomAD >0.00006, an odds ratio of ≥2.08 when comparing MH case points to allele count in gnomAD can qualify. Popmax in gnomAD must be <0.0038.
No qualifying assumed de novo case is documented for RYR1 c.1840C>T. The available evidence contains inherited family observations and no case-level parental testing or clinical documentation sufficient to establish an assumed de novo event. The VCEP point-based PM6 rule therefore cannot be evaluated.
The VCEP specifies PP1 as Supporting for co-segregation in 3-4 reported meioses, Moderate for 5-6, and Strong for at least 7. The reviewed evidence documents R614C in multiple malignant hyperthermia families and genotype-phenotype assessment by IVCT, but the available extracts do not provide an exact count of disease-cosegregating meioses. Therefore, no PP1 strength can be assigned without extrapolating beyond the reported evidence.
The VCEP requires either two or more variant-positive individuals with a negative IVCT/CHCT test for strong BS2, or one variant-positive individual with a negative IVCT/CHCT test for moderate BS2, in the context of a healthy adult and full penetrance expected at an early age. The available RYR1 Arg614Cys literature documents affected or test-characterized families and an R614C homozygote, but does not document a healthy adult R614C carrier with a negative IVCT/CHCT result. gnomAD reports zero homozygotes, but population homozygote absence does not establish the VCEP's required healthy-adult negative-test evidence.
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. * Two or more variant positive individuals with a negative IVCT/CHCT test ... 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. * One variant positive individual with a negative IVCT/CHCT test
No available study provides VCEP-calibrated benign functional evidence for R614C. The available variant-specific functional study instead reports increased agonist sensitivity and abnormal calcium handling, while the IVCT study reports stronger contracture effects. Neither documents no significant calcium release or no increased RYR1-agonist sensitivity under the VCEP's required in-vitro, ex-vivo, or knock-in-mouse conditions. BS3 is therefore not assessed, not assigned a benign strength, and not treated as contradicted evidence because the VCEP rule cannot be evaluated to a qualifying benign endpoint from the available studies.
Well-established functional studies show no damaging effect on protein function * Three or more independent ex vivo studies, NO significant release of Ca2+ in response to agonist...Well-established functional studies show no damaging effect on protein function * No significant increased sensitivity to RYR1 agonist in an approved in vitro assay, Ca2+ release measured, n≥3 * One or two independent ex vivo studies, NO significant release of Ca2+ in response to agonist * Knock-in mouse showing no MH reaction in response to RYR1 agonist AND no increased sensitivity to RYR1 agonists in ex vivo tissue/cells
The VCEP BP2 rule requires the assessed variant to be observed in cis with a pathogenic variant in any inheritance pattern. The available variant-specific paper reports RYR1 p.Arg614Cys and R2454C in the same probands as compound heterozygous variants inherited from different parents, which is trans rather than cis; it does not establish the assessed variant in cis with a pathogenic variant. Because no qualifying cis observation is documented in the available evidence, BP2 cannot be evaluated as met or not met.
Observed in cis with a pathogenic variant in any inheritance pattern
The ClinGen Malignant Hyperthermia Susceptibility Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RYR1 Version 2.0 marks PVS1 as not applicable. The VCEP states: "PVS1 is not applicable. MHS is due to gain of function variants in RYR1." NM_000540.3:c.1840C>T in RYR1 is a missense substitution predicted to produce NP_000531.2:p.(Arg614Cys). This determination was made deterministically from the VCEP criteria specification, prior to LLM adjudication.
deterministic_prefilter: vcep_not_applicable
The RYR1 VCEP explicitly marks PM2 as not applicable. No PM2 evidence is assigned regardless of the observed gnomAD frequencies.
Not Applicable
The ClinGen Malignant Hyperthermia Susceptibility Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RYR1 Version 2.0 expressly exclude PM3 because malignant hyperthermia susceptibility is an autosomal dominant disorder with reduced penetrance. Therefore, the reported homozygous or compound-heterozygous observations for RYR1 p.Arg614Cys do not permit PM3 application under this VCEP framework.
PM3 is not applicable. MHS is inherited as an autosomal dominant trait with reduced penetrance.
The ClinGen Malignant Hyperthermia Susceptibility Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RYR1 Version 2.0 marks PM4 as not applicable. The VCEP states: "PM4 is not applicable. The majority of RYR1 variants that are causative for MHS are missense variants." NM_000540.3:c.1840C>T in RYR1 is a missense substitution predicted to produce NP_000531.2:p.(Arg614Cys). This determination was made deterministically from the VCEP criteria specification, prior to LLM adjudication.
deterministic_prefilter: vcep_not_applicable
The RYR1 VCEP explicitly marks PP2 as not applicable because RYR1 does not appear constrained for missense variation, citing a gnomAD missense constraint z-score of 1.92.
PP2 is not applicable. RYR1 does not appear to be constrained for missense variation with a z-score of 1.92 in gnomAD.
The RYR1 VCEP explicitly excludes PP4 because CACNA1S variants can also cause malignant hyperthermia susceptibility; no phenotype-specific PP4 evidence can therefore be applied under this VCEP.
PP4 is not applicable, variants in CACNA1S also result in MHS.
The RYR1 VCEP explicitly excludes BS4 because MHS phenotype is determined using IVCT or CHCT, IVCT has an approximately 6% false-positive rate, and phenotype cannot be reliably determined in individuals without an MH crisis.
BS4 is not applicable. Phenotype for MHS is routinely determined based on the vitro contraction test (IVCT) that has a false positive rate of approximately 6% (PP1) or the caffeine-halothane contracture test (CHCT). As the phenotype in individuals who have not experienced an MH crisis cannot be reliably determined BS4 is not utilized.
The RYR1 VCEP explicitly marks BP1 as not applicable because malignant hyperthermia is caused primarily by missense variants in RYR1.
BP1 is not applicable. MH is caused primarily by missense variants in RYR1.
The ClinGen Malignant Hyperthermia Susceptibility Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RYR1 Version 2.0 marks BP3 as not applicable. The VCEP states: "BP3 is not applicable. RYR1 does not have repetitive regions without known function." NM_000540.3:c.1840C>T in RYR1 is a missense substitution predicted to produce NP_000531.2:p.(Arg614Cys). This determination was made deterministically from the VCEP criteria specification, prior to LLM adjudication.
deterministic_prefilter: vcep_not_applicable
The RYR1 VCEP marks BP5 as not applicable because individuals have been described with MHS and two pathogenic RYR1 variants; an alternate molecular basis cannot be used for BP5 in this framework.
BP5 is not applicable as individuals have been described with MHS and two pathogenic variants in RYR1.
The RYR1 VCEP marks BP6 as not applicable and states that this criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.
This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.
BP7 is limited by the VCEP rule to synonymous (silent) variants. NM_000540.3:c.1840C>T is a missense variant producing p.Arg614Cys, so BP7 is outside its own scope and is not evaluated from splice or conservation predictions.
A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Every interpreted variant in RYR1, mapped onto the exon structure of NM_000540.3. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| European (Finnish)7 / 63,998 | 0.00011 |
| Remaining individuals6 / 62,508 | 9.6e-05 |
| European (non-Finnish)104 / 1,180,012 | 8.8e-05 |
| African/African American1 / 74,992 | 1.3e-05 |
| European (non-Finnish)25 / 129,186 | 0.00019 |
| Remaining individuals1 / 7,226 | 0.00014 |
| European (Finnish)3 / 25,122 | 0.00012 |
| East Asian1 / 19,952 | 5e-05 |
This variant is present in gnomAD v4.1 (AF= 7.31078e-05; MAF= 0.00731%, 118/1614054 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.000109378; MAF= 0.01094%, 7/63998 alleles, homozygotes = 0); grpmax FAF= 7.408e-05.
This variant is present in gnomAD v2.1 (AF= 0.000106059; MAF= 0.01061%, 30/282862 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000193519; MAF= 0.01935%, 25/129186 alleles, homozygotes = 0); grpmax FAF= 0.00021229.
This variant is present in gnomAD-Canada v1.0 (AF= 0.0001086484137331595, 2/18408 alleles, homozygotes = 0).
The variant is a missense SNV, so the VCEP's PP3 missense computational path applies. That path names REVEL and specifies a score greater than 0.85; the case-specific REVEL score is 0.927, which meets the VCEP threshold. No splice predictor or other computational predictor is counted for PP3 because the governing rule names REVEL for this path.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product ... * Use REVEL score of >0.85
The variant is a missense SNV and therefore is within the VCEP's BP4 computational scope. The governing rule names REVEL and requires a score below 0.5 for no computational impact. The case-specific REVEL score is 0.927, so the BP4 threshold is not met. SpliceAI is not counted because the VCEP BP4 rule names REVEL, not SpliceAI, for this situation.
Computational evidence suggest no impact on gene or gene product, REVEL score of <0.5
BP7 is limited by the VCEP rule to synonymous (silent) variants. NM_000540.3:c.1840C>T is a missense variant producing p.Arg614Cys, so BP7 is outside its own scope and is not evaluated from splice or conservation predictions.
A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). REVEL score = 0.927. BayesDel score = 0.458335.
10 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Mutation R614C was found in 3 families (6%) and mutation G2434R in 2 families (4%). Mutation R2458C was present in one family (2%). No homozygous mutation carriers were found.
Results, Mutation frequency; Table 2; Discussion, genotype-phenotype comparison
Mutation screening of the RyR1 gene revealed the presence of the “pig” mutation, i.e., the R614C mutation, in his mother’s DNA (patient I-2) and of the R2454C mutation in his father’s DNA, while proband II-1 and his brother (patient II-2) were compound heterozygous bearing both R614C and R2454C mutations (fig. 1).
Results, Family Li200; additional relevant observations in Results, Families Li137 and Li53, and Discussion
Myotubes expressing any RyR1 were significantly more sensitive to stimulation by caffeine and 4-CmC than those expressing WT RyR1.
Abstract; Results, Myotubes Expressing MHRyR1s Have Heightened Sensitivity to Depolarization and Direct Channel Agonists; Figs. 2-4
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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= 7.31078e-05; MAF= 0.00731%, 118/1614054 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.000109378; MAF= 0.01094%, 7/63998 alleles, homozygotes = 0); grpmax FAF= 7.408e-05.
This variant is present in gnomAD v2.1 (AF= 0.000106059; MAF= 0.01061%, 30/282862 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000193519; MAF= 0.01935%, 25/129186 alleles, homozygotes = 0); grpmax FAF= 0.00021229.
This variant is present in gnomAD-Canada v1.0 (AF= 0.0001086484137331595, 2/18408 alleles, homozygotes = 0).
This variant has been reported in ClinVar as Pathogenic (27 clinical laboratories) and as pathogenic (1 clinical laboratory) and as drug response by ClinPGx (expert panel) and as Pathogenic by ClinGen Malignant Hyperthermia Susceptibility Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 12964)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). REVEL score = 0.927. BayesDel score = 0.458335.
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV100616513, n = 1 times).
This variant does not lie in a statistically significant hotspot.