The RYR1 NM_000540.3:c.7300G>A (NP_000531.2:p.(Gly2434Arg)) missense variant has previously been reported in somatic cancers (COSMIC; COSV62092833, n = 4 times). Based on available guidelines, this variant is considered to be Likely Pathogenic. This variant is considered to be drug response by the VCEP (ClinPGx; ClinVar ID 12970).
Five-step scale from benign to pathogenic. This variant is likely pathogenic. Select a step to read what it means.
Likely pathogenic.A likely 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.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 strong: 7 MH case points and computed OR 738.94 (95% CI 337.82–1,616.35) exceed the VCEP's >=18.7 threshold with popmax FAF 0.00010959 <0.0038.
Met at moderate: residue 2434 lies within the VCEP-approved central PM1 region 2,101-2,458, and PS1 or PM5 is not applied.
Met (moderate): REVEL 0.965 exceeds the VCEP's >0.85 threshold for computational evidence supporting a deleterious effect.
Not applicable: the RYR1 VCEP explicitly marks PP5 as Not Applicable.
No benign criterion marked as applied in the recorded assessment.
Likely Pathogenic: PS4 (strong) plus PM1 and PP3 (moderate), with PP5 (supporting), satisfy ACMG/AMP Table 5.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 156 / 1,614,004 alleles. Recorded AF 9.6654e-05. Recorded homozygote count 0.
This variant is present in gnomAD v2.1 (AF= 3.89177e-05; MAF= 0.00389%, 11/282648 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 7.75074e-05; MAF= 0.00775%, 10/129020 alleles, homozygotes = 0); grpmax FAF= 3.423e-05.
Not available in gnomAD-Canada v1.0.
Recorded REVEL score: 0.965. Refer to the recorded PP3/BP4 rationale for interpretation.
30 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; COSV62092833, n = 4 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: 4 met · 4 not met · 8 not assessed · 12 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Only PS1, PM1, PM5, PP2, and BP1 were adjudicated under the RYR1 VCEP Version 2.0 rules.
PM1 is met at moderate strength because residue 2434 lies in the specified 2,101-2,458 central region; PS1 and PM5 were not applied, so the VCEP downgrade condition is not triggered.
PS2 and PM6 are not assessed because no proven or assumed de novo cases with the required parental evidence are documented.
PP1 is not assessed because cosegregation is reported but the qualifying meiosis count required by the VCEP is unavailable.
BS4 is not applicable under the RYR1 VCEP specification.
PS4 is met at Strong because the VCEP's alternate case-control path applies: popmax FAF 0.00010959 is >0.00006 and <0.0038, and the computed OR 738.94 satisfies the exact >=18.7 operator.
PP4, PP5, BP5, and BP6 are not applicable because the RYR1 VCEP CSPEC explicitly marks each criterion Not Applicable.
PM3 is not applicable under the RYR1 MHS VCEP specification.
BP2 is not assessed because cis phase with another pathogenic variant is not documented.
No criteria match.
The RYR1 VCEP PS4 Strong rule requires either at least 7 MH case points with popmax <=0.00006, or, when popmax MAF is >0.00006, an odds ratio >=18.7 comparing MH case points with gnomAD allele count and popmax <0.0038. Brandt et al. report Gly-2434-Arg in 7 of 105 unrelated MHS individuals/families, supplying 7 MH case points. gnomAD v4.1 reports popmax FAF 0.00010959, so the alternate path applies: 0.00010959 > 0.00006, and 0.00010959 < 0.0038. Using 7 variant-positive cases and 98 variant-negative cases versus 156 variant alleles and 1,613,848 nonvariant alleles in gnomAD v4.1, I computed OR = (7 x 1,613,848)/(98 x 156) = 738.94, 95% CI 337.82-1,616.35; therefore 738.94 >= 18.7 and PS4 Strong is met. The exact p.Gly2434Arg is independently reported in additional MHS cohorts and affected families, including 4/73 North American MHS individuals, 2/48 Swiss MHS families, and affected families with rhabdomyolysis/exertional myalgia.
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 queried variant is p.Gly2434Arg, so its residue is 2434. The RYR1 VCEP PM1 moderate region explicitly includes residues 2,101-2,458 (central region), which contains residue 2434. The VCEP also states that PM1 should not be moderate when PS1 or PM5 is applied; neither PS1 nor PM5 is applied here. The VCEP domain_tables entry is empty, so there is no additional authoritative domain-table restriction to check.
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.
The VCEP PP3 rule applies to computational evidence supporting a deleterious effect and specifically requires REVEL >0.85 for the applicable missense variant path. NM_000540.3:c.7300G>A is a missense variant, p.(Gly2434Arg), and the recorded REVEL score is 0.965, exceeding the VCEP cutoff. No splice-prediction result is counted for PP3 because the governing PP3 rule names REVEL for this situation; the same REVEL result is not reused for BP4.
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.
Not Applicable
The RYR1 VCEP specifies BA1 when the popmax allele frequency is >0.0038 (0.38%). Using the default all-comers gnomAD source because the VCEP does not specify a non-cancer or exome-only source, the highest reported popmax FAF is 0.00010959 (0.010959%) in gnomAD v4.1, below 0.0038; gnomAD v2.1 reports grpmax FAF 0.00003423. Therefore BA1 is not met.
Popmax allele frequency >0.0038 (0.38%)
The RYR1 VCEP specifies BS1 at strong strength when the popmax allele frequency is >0.0008 (0.08%). Using the default all-comers gnomAD source because the VCEP does not specify a non-cancer or exome-only source, the highest reported popmax FAF is 0.00010959 (0.010959%) in gnomAD v4.1, below 0.0008; gnomAD v2.1 reports grpmax FAF 0.00003423. Therefore BS1 is not met.
Popmax allele frequency >0.0008 (0.08%)
The variant-specific study in PMID:10700782 reports increased, faster ryanodine-stimulated intracellular Ca2+ responses in primary skeletal-muscle myotubes from four carriers compared with four controls, rather than no damaging effect. This directly conflicts with the premise of BS3. The evidence does not satisfy either VCEP benign functional path: it is not a study showing no significant increased sensitivity in an approved in vitro assay with measured Ca2+ release and n≥3, nor does it show one or more independent ex vivo studies with no significant Ca2+ release.
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 BP4 rule requires computational evidence suggesting no impact on the gene or gene product and a REVEL score <0.5. This variant is missense, so BP4 is within the rule's protein-impact scope, but its REVEL score is 0.965, not <0.5. The score therefore does not support BP4; the SpliceAI no-impact result is not used to override the missense REVEL requirement and is not double-counted with PP3.
Computational evidence suggest no impact on gene or gene product, REVEL score of <0.5
The VCEP requires the same amino-acid change as a previously established pathogenic variant, with that prior variant reaching pathogenic classification without PS1. The available reports describe Gly2434Arg under differing historical coding or protein-numbering conventions, including G7303A and Gly2435Arg, but do not establish that either is a distinct nucleotide change from NM_000540.3:c.7300G>A. The evidence therefore cannot verify an independent previously established pathogenic variant satisfying PS1.
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
The available case evidence does not document any proven or assumed de novo occurrence of RYR1 NM_000540.3:c.7300G>A/p.(Gly2434Arg), nor does it provide parental maternity and paternity testing for a de novo case. Therefore, no PS2 points or strength can be assigned under the VCEP point-based rule.
Each proven de novo case, 2 points, each assumed de novo case, 1 point, ≥8 points ... Each proven de novo case, 2 points, each assumed de novo case, 1 point, a total of 4-7 points ... Each proven de novo case, 2 points, each assumed de novo case, 1 point, a total of 2-3 points ... Each proven de novo case, 2 points, each assumed de novo case, 1 point, a total of 1 point
The VCEP's applicable PS3 paths require either a specified knock-in mouse result, a HEK293 assay with significantly increased Ca2+ release versus WT, known pathogenic and benign controls, and n≥3, three or more independent ex vivo studies showing Ca2+ release in response to an RYR1 agonist, or two independent ex vivo studies showing that result. PMID:10700782 reports increased ryanodine-induced Ca2+ responses in primary myotubes from four Gly2435Arg/Gly2434Arg carriers versus four controls, but it is one ex vivo study. PMID:19648156 summarizes prior heightened sensitivity but does not provide an independent variant-specific Ca2+ release experiment, and PMID:10484775 reports IVCT contractures rather than the VCEP-specified Ca2+ release assay. The available evidence does not document the required HEK293 controls and sample size, and the separate knock-in-mouse lead is not independently auditable in the available source material. Therefore no PS3 strength can be assigned.
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 VCEP PM5 rule requires a different missense variant at the same amino-acid residue that was previously determined to be pathogenic without PM5; moderate strength additionally requires the alternate pathogenic variant's Grantham score to be lower than the assessed variant's. The available same-residue search found no comparator candidates, and the supplied literature reports Gly2434Arg itself rather than a different missense change at residue 2434. Therefore the required comparator and Grantham comparison are unavailable.
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 available case evidence does not document any assumed de novo occurrence of RYR1 NM_000540.3:c.7300G>A/p.(Gly2434Arg) in a patient with the relevant disease and without confirmed parental testing. Consequently, the VCEP PM6 point total cannot be calculated.
Each proven de novo case, 2 points, each assumed de novo case, 1 point, ≥8 points ... Each proven de novo case, 2 points, each assumed de novo case, 1 point, a total of 4-7 points ... Each proven de novo case, 2 points, each assumed de novo case, 1 point, a total of 2-3 points ... Each proven de novo case, 2 points, each assumed de novo case, 1 point, a total of 1 point
PMID:11575529 reports cosegregation of Gly2434Arg with a positive CHCT phenotype in selected families, including a proband and mother who were both mutation-positive and CHCT-positive, but the available extracted evidence does not report the number of qualifying meioses. The VCEP threshold for PP1 strength therefore cannot be applied.
Co-segregation with disease in ≥7 reported meioses ... Co-segregation with disease in 5-6 reported meioses ... Co-segregation with disease in 3-4 reported meioses
The VCEP BS2 rule requires observation in a healthy adult with full penetrance expected at an early age, with strong evidence requiring two or more variant-positive individuals with a negative IVCT/CHCT test or moderate evidence requiring one such individual. Population data show zero homozygotes in gnomAD v2.1 and v4.1, but do not establish healthy adult status, heterozygosity, or negative IVCT/CHCT testing for named individuals. The available evidence is therefore insufficient to assess 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. ... * Two or more variant positive individuals with a negative IVCT/CHCT test
The VCEP BP2 rule requires the evaluated variant to be observed in cis with a pathogenic variant in any inheritance pattern. The available case evidence reports affected individuals and familial observations for p.Gly2434Arg, but does not document a second pathogenic variant in cis or establish cis phase with one. Because the required phase and pathogenic-variant evidence are unavailable, BP2 cannot be evaluated.
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.7300G>A in RYR1 is a missense substitution predicted to produce NP_000531.2:p.(Gly2434Arg). This determination was made deterministically from the VCEP criteria specification, prior to LLM adjudication.
deterministic_prefilter: vcep_not_applicable
The RYR1 VCEP marks PM2 as not applicable for this VCEP and explicitly states that PM2 is not used alone. No PM2 evidence is assigned.
PM2 is not used alone.
PM3 is not applicable under the RYR1 Malignant Hyperthermia Susceptibility VCEP specification because MHS is inherited as an autosomal dominant trait with reduced penetrance. The VCEP explicitly marks PM3 as not applicable; therefore, no trans-phase or affected-proband evidence can activate this criterion.
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.7300G>A in RYR1 is a missense substitution predicted to produce NP_000531.2:p.(Gly2434Arg). 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 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 CSPEC marks PP4 as Not Applicable. No generic PP4 phenotype-specificity rule was substituted.
Not Applicable
The RYR1 VCEP explicitly designates BS4 as not applicable because MHS phenotype determination relies on IVCT or CHCT, IVCT has an approximately 6% false-positive rate, and phenotype cannot be reliably determined in individuals without an MH crisis. This criterion is not used regardless of the reported non-segregation observation in PMID:10484775.
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 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.7300G>A in RYR1 is a missense substitution predicted to produce NP_000531.2:p.(Gly2434Arg). This determination was made deterministically from the VCEP criteria specification, prior to LLM adjudication.
deterministic_prefilter: vcep_not_applicable
The RYR1 VCEP CSPEC marks BP5 as Not Applicable. No alternative benign-rule threshold was substituted.
Not Applicable
The RYR1 VCEP CSPEC marks BP6 as Not Applicable. No benign assertion from a laboratory or database was used as BP6 evidence.
Not Applicable
The VCEP BP7 rule is limited to synonymous (silent) variants. NM_000540.3:c.7300G>A produces the missense consequence p.(Gly2434Arg), so BP7 is outside its governing scope and is not_applicable before splice-prediction or conservation evidence is considered.
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 (non-Finnish)149 / 1,180,014 | 0.00013 |
| Remaining individuals5 / 62,488 | 8e-05 |
| African/African American2 / 74,928 | 2.7e-05 |
| European (non-Finnish)10 / 129,020 | 7.8e-05 |
| African/African American1 / 24,956 | 4e-05 |
This variant is present in gnomAD v4.1 (AF= 9.6654e-05; MAF= 0.00967%, 156/1614004 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.00012627; MAF= 0.01263%, 149/1180014 alleles, homozygotes = 0); grpmax FAF= 0.00010959.
This variant is present in gnomAD v2.1 (AF= 3.89177e-05; MAF= 0.00389%, 11/282648 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 7.75074e-05; MAF= 0.00775%, 10/129020 alleles, homozygotes = 0); grpmax FAF= 3.423e-05.
Not available in gnomAD-Canada v1.0.
The VCEP PP3 rule applies to computational evidence supporting a deleterious effect and specifically requires REVEL >0.85 for the applicable missense variant path. NM_000540.3:c.7300G>A is a missense variant, p.(Gly2434Arg), and the recorded REVEL score is 0.965, exceeding the VCEP cutoff. No splice-prediction result is counted for PP3 because the governing PP3 rule names REVEL for this situation; the same REVEL result is not reused for BP4.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product * Use REVEL score of >0.85
The VCEP BP4 rule requires computational evidence suggesting no impact on the gene or gene product and a REVEL score <0.5. This variant is missense, so BP4 is within the rule's protein-impact scope, but its REVEL score is 0.965, not <0.5. The score therefore does not support BP4; the SpliceAI no-impact result is not used to override the missense REVEL requirement and is not double-counted with PP3.
Computational evidence suggest no impact on gene or gene product, REVEL score of <0.5
The VCEP BP7 rule is limited to synonymous (silent) variants. NM_000540.3:c.7300G>A produces the missense consequence p.(Gly2434Arg), so BP7 is outside its governing scope and is not_applicable before splice-prediction or conservation evidence is considered.
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 = 0.00). REVEL score = 0.965. BayesDel score = 0.567204.
8 paper records listed. 6 cited in the classification.
Screening of 105 unrelated MHS individuals for all known RYR1 mutations (Table 1) revealed base exchanges in 23 MH families resulting in the following amino acid substitutions: Arg-614-Cys in nine patients, Arg-614-Leu in one, Arg-2163-Cys in one, Val-2168-Met in one, Thr-2206-Met in three, Gly-2434-Arg in seven and Arg-2454-His in one.
Location Results, Screening for known mutations; Table 1; Table 3
Context Screening of 105 unrelated malignant-hyperthermia-susceptible individuals from 95 MH and 10 CCD families, with IVCT phenotyping.
The most common mutation was Gly2434Arg, occurring in four patients and accounting for 5.5% of the population, followed by Arg2454His in three patients (4.1%) and Arg163Cys in two patients (2.7%).
Location Results, Distribution of RYR1 Mutations in North American Malignant Hyperthermia Population; Table 1; Table 2
Context RYR1 screening in 73 unrelated North American individuals diagnosed as malignant-hyperthermia susceptible by caffeine-halothane contracture testing.
Mutation R614C was found in 3 families (6%) and mutation G2434R in 2 families (4%). Mutation R2458C was present in one family (2%).
Location Results, Mutation frequency; Table 2; Abstract
Context Swiss malignant-hyperthermia cohort of 48 unrelated families with RYR1 mutation screening and in vitro contracture testing.
This variant has been functionally characterized and shown to have a heightened sensitivity to activating concentrations of Ca2+ and to caffeine and 4-chloro-m-cresol in vitro.
Location Results, "RYR1 genotype–IVCT phenotype correlation"; Table 3; Table 4
Context UK MH Investigation Unit cohort with quantitative caffeine, halothane, and ryanodine IVCT assays; p.G2434R was used as a comparator and prior functional results were summarized.
In Family 7, both mother (7.I.1, on the right) and daughter (7.II.2, centre) presented with recurrent episodes of rhabdomyolysis and were found to carry the same heterozygous RYR1 missense mutation, p.Gly2434Arg.
Location Figure 1 caption; Results, section 3.3; Table 2, Families 7–8
Context RYR1 sequencing in 39 unrelated families presenting with exertional myalgia and/or rhabdomyolysis, with familial testing and comparison to 1000 Genomes and EVS population datasets.
Several years later he underwent genetic testing, and he was found to have a known causative MH mutation in RYR1 (p.Gly2434Arg).
Location Table 3; Appendix, Case B—Airway Rescue in the Emergency Department and Case D—Electroconvulsive Therapy in Treatment Suite
Context Retrospective study of 129 CHCT-confirmed MHS probands; RYR1 mutation analysis was available for 51 individuals, with detailed clinical case summaries.
PCR analysis revealed that the four MHS individuals were heterozygous for the Gly2435Arg mutation of the RYR1 gene.
Patients and methods, Patients; Results, MHS myotubes: resting Ca2+ concentrations and effects of ryanodine at 37°C
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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= 9.6654e-05; MAF= 0.00967%, 156/1614004 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.00012627; MAF= 0.01263%, 149/1180014 alleles, homozygotes = 0); grpmax FAF= 0.00010959.
This variant is present in gnomAD v2.1 (AF= 3.89177e-05; MAF= 0.00389%, 11/282648 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 7.75074e-05; MAF= 0.00775%, 10/129020 alleles, homozygotes = 0); grpmax FAF= 3.423e-05.
Not available in gnomAD-Canada v1.0.
This variant has been reported in ClinVar as Pathogenic (30 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 = 12970)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.965. BayesDel score = 0.567204.
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV62092833, n = 4 times).
This variant does not lie in a statistically significant hotspot.