ClinVar Genomic variation as it relates to human health
NM_000540.3(RYR1):c.1201C>T (p.Arg401Cys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000540.3(RYR1):c.1201C>T (p.Arg401Cys)
Variation ID: 133029 Accession: VCV000133029.33
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 19q13.2 19: 38451842 (GRCh38) [ NCBI UCSC ] 19: 38942482 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jun 9, 2014 Apr 20, 2024 Mar 29, 2022 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000540.3:c.1201C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000531.2:p.Arg401Cys missense NM_001042723.2:c.1201C>T NP_001036188.1:p.Arg401Cys missense NC_000019.10:g.38451842C>T NC_000019.9:g.38942482C>T NG_008866.1:g.23143C>T LRG_766:g.23143C>T LRG_766t1:c.1201C>T LRG_766p1:p.Arg401Cys P21817:p.Arg401Cys - Protein change
- R401C
- Other names
- NM_000540.3(RYR1):c.1201C>T
- Canonical SPDI
- NC_000019.10:38451841:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
RYR1 | No evidence available | No evidence available |
GRCh38 GRCh37 |
8820 | 9127 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Jul 3, 2023 | RCV000119449.19 | |
Pathogenic (1) |
criteria provided, single submitter
|
Mar 22, 2024 | RCV000610923.8 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jan 4, 2024 | RCV000802489.7 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Feb 19, 2018 | RCV001266973.3 | |
Pathogenic (4) |
reviewed by expert panel
|
Mar 29, 2022 | RCV001822999.5 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV003227643.2 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV003227645.2 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV003227646.2 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV003227647.2 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV003227648.2 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV003227642.2 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV003227644.2 | |
click to load more click to collapse |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(Mar 29, 2022)
|
reviewed by expert panel
Method: curation
|
Malignant hyperthermia, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen Malignant Hyperthermia Susceptibility Variant Curation Expert Panel, ClinGen
Accession: SCV002570147.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
This pathogenicity assessment is relevant only for malignant hyperthermia susceptibility (MHS) inherited in an autosomal dominant pattern. Variants in RYR1 can also cause other myopathies … (more)
This pathogenicity assessment is relevant only for malignant hyperthermia susceptibility (MHS) inherited in an autosomal dominant pattern. Variants in RYR1 can also cause other myopathies inherited in an autosomal dominant pattern or in an autosomal recessive pattern. Some of these disorders may predispose individuals to malignant hyperthermia. RYR1 variants may also contribute to a malignant hyperthermia reaction in combination with other genetic and non-genetic factors and the clinician needs to consider such factors in making management decisions. This sequence variant predicts a substitution of arginine with cysteine at codon 401 of the RYR1 protein p.(Arg401Cys). The maximum allele frequency for this variant among the six major gnomAD populations is EAS: 0.00005, a frequency consistent with pathogenicity for MHS. This variant has been reported in five unrelated individuals who have a personal or family history of a malignant hyperthermia reaction and a positive in vitro contracture test (IVCT) or caffeine halothane contracture test (CHCT) result (when the proband was unavailable for testing a positive diagnostic test result in a mutation positive relative was counted), PS4_Moderate ( PMID:30236257, PMID:12434264, PMID:24433488, PMID:25735680). This variant segregates with MHS in three individuals, PP1 (PMID:12066726, PMID:18564801). Functional studies in HEK293 cells show an increased sensitivity to RYR1 agonists PS3_Moderate, (PMID:23459219). Another variant has been assessed as pathogenic occurs at this codon, p.(Arg401His), PM5 (PMID:16917943). This variant resides in a region of RYR1 considered to be a hotspot for pathogenic variants that contribute to MHS, use PM1_Supporting to avoid overweighting with PM5 (PMID: 21118704). A REVEL score > 0.85 (0.886) supports pathogenicity, PP3_Moderate. Criteria implemented: PS4_Moderate, PS3_Moderate, PM1_Supporting, PM5, PP1, PP3_Moderate. Based on using Bayes to combine criteria this variant is assessed as Pathogenic, (PMID: 29300386). (less)
|
|
drug response
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
|
enflurane response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV003925497.1
First in ClinVar: May 20, 2023 Last updated: May 20, 2023 |
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or … (more)
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. (less)
|
|
drug response
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
|
desflurane response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV003925496.1
First in ClinVar: May 20, 2023 Last updated: May 20, 2023 |
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or … (more)
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. (less)
|
|
drug response
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
|
halothane response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV003925498.1
First in ClinVar: May 20, 2023 Last updated: May 20, 2023 |
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or … (more)
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. (less)
|
|
drug response
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
|
isoflurane response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV003925499.1
First in ClinVar: May 20, 2023 Last updated: May 20, 2023 |
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or … (more)
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. (less)
|
|
drug response
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
|
methoxyflurane response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV003925500.1
First in ClinVar: May 20, 2023 Last updated: May 20, 2023 |
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or … (more)
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. (less)
|
|
drug response
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
|
sevoflurane response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV003925501.1
First in ClinVar: May 20, 2023 Last updated: May 20, 2023 |
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or … (more)
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. (less)
|
|
drug response
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
|
succinylcholine response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV003925502.1
First in ClinVar: May 20, 2023 Last updated: May 20, 2023 |
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or … (more)
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. (less)
|
|
Pathogenic
(Jun 12, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000852278.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 |
|
|
Likely pathogenic
(May 26, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: yes
Allele origin:
germline
|
AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002501143.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Secondary finding: no
|
|
Uncertain significance
(Feb 19, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: yes
Allele origin:
germline
|
Ambry Genetics
Accession: SCV001445154.2
First in ClinVar: Nov 21, 2020 Last updated: Jan 07, 2023 |
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: Caucasian/Hispanic/Mexican/Italian/French/Dutch/English/Scottish/Irish
|
|
Pathogenic
(Nov 10, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV002512915.2
First in ClinVar: May 21, 2022 Last updated: Mar 04, 2023 |
Comment:
In addition to malignant hyperthermia susceptibility, some individuals who harbored the R401C variant presented with additional neuromuscular features including muscle cramps, multicore/minicore myopathy, and elevated … (more)
In addition to malignant hyperthermia susceptibility, some individuals who harbored the R401C variant presented with additional neuromuscular features including muscle cramps, multicore/minicore myopathy, and elevated CK levels (Davis et al., 2002; Galli et al., 2002); Functional analysis of R401C shows that it leads to higher sensitivity to agonist compared to wildtype controls (Sato et al., 2013); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30236257, 28326467, 14999498, 32381029, 25735680, 23459219, 23919265, 29635721, 24433488, 16917943, 28818389, 12208234, 18564801, 12434264, 23553484, 12066726, 31589614) (less)
|
|
Pathogenic
(Jul 03, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002019917.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
Pathogenic
(Jan 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Malignant hyperthermia, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV002072555.1
First in ClinVar: Feb 03, 2022 Last updated: Feb 03, 2022 |
Comment:
_x000D_ Criteria applied: PS3, PS4_MOD, PM1, PM5_STR, PM2_SUP, PP1, PP3
|
|
Pathogenic
(Jan 04, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
RYR1-Related Disorders
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000942323.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 401 of the RYR1 protein … (more)
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 401 of the RYR1 protein (p.Arg401Cys). This variant is present in population databases (rs193922764, gnomAD 0.005%). This missense change has been observed in individual(s) with autosomal dominant malignant hyperthermia susceptibility and/or autosomal recessive RYR1-related myopathy (PMID: 12066726, 23919265, 24433488, 25735680, 28818389, 30236257). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 133029). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RYR1 protein function. Experimental studies have shown that this missense change affects RYR1 function (PMID: 23459219). This variant disrupts the p.Arg401 amino acid residue in RYR1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12059893, 24433488; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Mar 30, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Malignant hyperthermia, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV004357275.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces arginine with cysteine at codon 401 of the RYR1 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces arginine with cysteine at codon 401 of the RYR1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant increases sensitivity to 4-CmC and caffeine compare to wild-type RYR1 in HEK293 cells (PMID: 23459219, 26115329, 31841587). This variant has been reported in at least 4 individuals affected with malignant hyperthermia clinical crises and in at least 4 families affected with malignant hyperthermia susceptibility (PMID: 12066726, 12066726, 12434264, 18564801, 24433488, 25735680, 30236257). It has been shown that this variant segregates with disease in two families (PMID: 12066726). This variant has been identified in 2/282746 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less)
|
|
Pathogenic
(Dec 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV002822555.8
First in ClinVar: Jan 21, 2023 Last updated: Apr 15, 2024 |
Comment:
RYR1: PM1, PM2, PM5, PS3:Moderate, PS4:Moderate, PP1
Number of individuals with the variant: 1
|
|
Pathogenic
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Malignant hyperthermia, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004820739.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
This missense variant replaces arginine with cysteine at codon 401 of the RYR1 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces arginine with cysteine at codon 401 of the RYR1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant increases sensitivity to 4-CmC and caffeine compare to wild-type RYR1 in HEK293 cells (PMID: 23459219, 26115329, 31841587). This variant has been reported in at least 4 individuals affected with malignant hyperthermia clinical crises and in at least 4 families affected with malignant hyperthermia susceptibility (PMID: 12066726, 12066726, 12434264, 18564801, 24433488, 25735680, 30236257). It has been shown that this variant segregates with disease in two families (PMID: 12066726). This variant has been identified in 2/282746 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less)
Number of individuals with the variant: 3
|
|
Pathogenic
(Mar 22, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Malignant hyperthermia of anesthesia
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000712043.4
First in ClinVar: Apr 09, 2018 Last updated: Apr 20, 2024 |
Comment:
proposed classification - variant undergoing re-assessment, contact laboratory
|
|
not provided
(-)
|
no classification provided
Method: not provided
|
not provided
Affected status: not provided
Allele origin:
unknown
|
Leiden Muscular Dystrophy (RYR1)
Accession: SCV000154356.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 |
|
|
click to load more click to collapse |
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Insights into channel modulation mechanism of RYR1 mutants using Ca2+ imaging and molecular dynamics. | Yamazawa T | The Journal of general physiology | 2020 | PMID: 31841587 |
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Potent Volatile Anesthetic Agents and Succinylcholine in the Context of RYR1 or CACNA1S Genotypes. | Gonsalves SG | Clinical pharmacology and therapeutics | 2019 | PMID: 30499100 |
Genetic epidemiology of malignant hyperthermia in the UK. | Miller DM | British journal of anaesthesia | 2018 | PMID: 30236257 |
Phenotype and genotype of muscle ryanodine receptor rhabdomyolysis-myalgia syndrome. | Witting N | Acta neurologica Scandinavica | 2018 | PMID: 29635721 |
Common and variable clinical, histological, and imaging findings of recessive RYR1-related centronuclear myopathy patients. | Abath Neto O | Neuromuscular disorders : NMD | 2017 | PMID: 28818389 |
Divergent Activity Profiles of Type 1 Ryanodine Receptor Channels Carrying Malignant Hyperthermia and Central Core Disease Mutations in the Amino-Terminal Region. | Murayama T | PloS one | 2015 | PMID: 26115329 |
Analysis of the entire ryanodine receptor type 1 and alpha 1 subunit of the dihydropyridine receptor (CACNA1S) coding regions for variants associated with malignant hyperthermia in Australian families. | Gillies RL | Anaesthesia and intensive care | 2015 | PMID: 25735680 |
Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study. | Klingler W | Orphanet journal of rare diseases | 2014 | PMID: 24433488 |
Genotype-phenotype correlations in recessive RYR1-related myopathies. | Amburgey K | Orphanet journal of rare diseases | 2013 | PMID: 23919265 |
Severe congenital RYR1-associated myopathy: the expanding clinicopathologic and genetic spectrum. | Bharucha-Goebel DX | Neurology | 2013 | PMID: 23553484 |
Exercise-induced rhabdomyolysis and stress-induced malignant hyperthermia events, association with malignant hyperthermia susceptibility, and RYR1 gene sequence variations. | Carsana A | TheScientificWorldJournal | 2013 | PMID: 23476141 |
Skeletal muscle ryanodine receptor mutations associated with malignant hyperthermia showed enhanced intensity and sensitivity to triggering drugs when expressed in human embryonic kidney cells. | Sato K | Anesthesiology | 2013 | PMID: 23459219 |
Dominant and recessive RYR1 mutations in adults with core lesions and mild muscle symptoms. | Duarte ST | Muscle & nerve | 2011 | PMID: 21674524 |
Identification of genetic mutations in Australian malignant hyperthermia families using sequencing of RYR1 hotspots. | Gillies RL | Anaesthesia and intensive care | 2008 | PMID: 18564801 |
Mutations in RYR1 in malignant hyperthermia and central core disease. | Robinson R | Human mutation | 2006 | PMID: 16917943 |
Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility. | Monnier N | Human mutation | 2005 | PMID: 16163667 |
Adult onset multi/minicore myopathy associated with a mutation in the RYR1 gene. | Pietrini V | Journal of neurology | 2004 | PMID: 14999498 |
[Current aspects of the diagnosis of malignant hyperthermia]. | Rüffert H | Der Anaesthesist | 2002 | PMID: 12434264 |
Mutations in the RYR1 gene in Italian patients at risk for malignant hyperthermia: evidence for a cluster of novel mutations in the C-terminal region. | Galli L | Cell calcium | 2002 | PMID: 12208234 |
Mutation screening in the ryanodine receptor 1 gene (RYR1) in patients susceptible to malignant hyperthermia who show definite IVCT results: identification of three novel mutations. | Rueffert H | Acta anaesthesiologica Scandinavica | 2002 | PMID: 12059893 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/61f449cf-05e9-4bd2-b696-05dcefd57769 | - | - | - | - |
https://www.pharmgkb.org/clinicalAnnotation/1449310234 | - | - | - | - |
https://www.pharmgkb.org/variant/PA166176176 | - | - | - | - |
click to load more click to collapse |
Text-mined citations for rs193922764 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.