ClinVar Genomic variation as it relates to human health
NM_000540.3(RYR1):c.7300G>A (p.Gly2434Arg)
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
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NM_000540.3(RYR1):c.7300G>A (p.Gly2434Arg)
Variation ID: 12970 Accession: VCV000012970.55
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19q13.2 19: 38499993 (GRCh38) [ NCBI UCSC ] 19: 38990633 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 May 12, 2024 Jul 11, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000540.3:c.7300G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000531.2:p.Gly2434Arg missense NM_001042723.2:c.7300G>A NP_001036188.1:p.Gly2434Arg missense NC_000019.10:g.38499993G>A NC_000019.9:g.38990633G>A NG_008866.1:g.71294G>A LRG_766:g.71294G>A LRG_766t1:c.7300G>A LRG_766p1:p.Gly2434Arg P21817:p.Gly2434Arg - Protein change
- G2434R
- Other names
- NM_000540.3(RYR1):c.7300G>A
- Canonical SPDI
- NC_000019.10:38499992:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00003
The Genome Aggregation Database (gnomAD) 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00006
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 | ||
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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. |
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RYR1 | No evidence available | No evidence available |
GRCh38 GRCh37 |
8840 | 9150 |
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. |
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Pathogenic (7) |
reviewed by expert panel
|
Jul 11, 2022 | RCV000013837.22 | |
Pathogenic (11) |
criteria provided, multiple submitters, no conflicts
|
Mar 1, 2023 | RCV000119698.37 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 24, 2024 | RCV000551243.16 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Feb 5, 2024 | RCV000612258.16 | |
desflurane response - Toxicity
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drug response (1) |
reviewed by expert panel
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Mar 24, 2021 | RCV001787719.10 |
enflurane response - Toxicity
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drug response (1) |
reviewed by expert panel
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Mar 24, 2021 | RCV001787720.10 |
halothane response - Toxicity
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drug response (1) |
reviewed by expert panel
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Mar 24, 2021 | RCV001787721.10 |
isoflurane response - Toxicity
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drug response (1) |
reviewed by expert panel
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Mar 24, 2021 | RCV001787722.10 |
sevoflurane response - Toxicity
|
drug response (1) |
reviewed by expert panel
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Mar 24, 2021 | RCV001787724.10 |
methoxyflurane response - Toxicity
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drug response (1) |
reviewed by expert panel
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Mar 24, 2021 | RCV001787723.10 |
succinylcholine response - Toxicity
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drug response (1) |
reviewed by expert panel
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Mar 24, 2021 | RCV001787725.10 |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 4, 2023 | RCV002288488.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 30, 2021 | RCV002513026.9 | |
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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. |
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drug response
Drug-variant association: Toxicity
(Mar 24, 2021)
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reviewed by expert panel
Method: curation
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desflurane response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV000925395.2
First in ClinVar: Jul 01, 2019 Last updated: Dec 12, 2021
Comment:
Drug is not necessarily used to treat response condition
|
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)
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drug response
Drug-variant association: Toxicity
(Mar 24, 2021)
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reviewed by expert panel
Method: curation
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enflurane response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
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PharmGKB
Accession: SCV000925396.2
First in ClinVar: Jul 01, 2019 Last updated: Dec 12, 2021
Comment:
Drug is not necessarily used to treat response condition
|
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)
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drug response
Drug-variant association: Toxicity
(Mar 24, 2021)
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reviewed by expert panel
Method: curation
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halothane response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
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PharmGKB
Accession: SCV000925397.2
First in ClinVar: Jul 01, 2019 Last updated: Dec 12, 2021
Comment:
Drug is not necessarily used to treat response condition
|
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)
|
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drug response
Drug-variant association: Toxicity
(Mar 24, 2021)
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reviewed by expert panel
Method: curation
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isoflurane response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV000925398.2
First in ClinVar: Jul 01, 2019 Last updated: Dec 12, 2021
Comment:
Drug is not necessarily used to treat response condition
|
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)
|
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drug response
Drug-variant association: Toxicity
(Mar 24, 2021)
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reviewed by expert panel
Method: curation
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methoxyflurane response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
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PharmGKB
Accession: SCV000925399.2
First in ClinVar: Jul 01, 2019 Last updated: Dec 12, 2021
Comment:
Drug is not necessarily used to treat response condition
|
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)
|
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drug response
Drug-variant association: Toxicity
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
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sevoflurane response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV000925400.2
First in ClinVar: Jul 01, 2019 Last updated: Dec 12, 2021
Comment:
Drug is not necessarily used to treat response condition
|
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)
|
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drug response
Drug-variant association: Toxicity
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
|
succinylcholine response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
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PharmGKB
Accession: SCV000925401.2
First in ClinVar: Jul 01, 2019 Last updated: Dec 12, 2021
Comment:
Drug is not necessarily used to treat response condition
|
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)
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Pathogenic
(Jul 11, 2022)
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reviewed by expert panel
Method: curation
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Malignant hyperthermia, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen Malignant Hyperthermia Susceptibility Variant Curation Expert Panel, ClinGen
FDA Recognized Database
Accession: SCV002570137.1 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 glycine with arginine at codon 2434 of the RYR1 protein, p.(Gly2434Arg). The maximum allele frequency for this variant among the six major gnomAD populations is NFE: 0.000078, a frequency consistent with pathogenicity for MHS. This variant has been reported in 178 unrelated individuals who have a personal or family history of a malignant hyperthermia reaction, 174 of these individuals had a positive in vitro contracture test (IVCT) or caffeine halothane contracture test (CHCT) result (if the proband was unavailable for testing, a positive diagnostic test result in a mutation-positive relative was counted, PS4 (PMID: 30236257, 10484775, 23558838, 16163667, 21455645, 23842196, 7849712, 7881417, 11575529, 15731587, 11668625, 12059893, 12151923, 31559918, 10700782, 17081125, 18564801, 20681998, 21965348, 23460944, 25735680, 25960145, 9030597, 25268394, 17667681). This variant has been identified in six individuals with negative IVCT/CHCT results, BS2 (PMID:30236257). A functional study in HEK293 cells shows an increased sensitivity to RYR1 agonists (PMID: 27586648). p.(Gly2434Arg) knock-in mice are susceptible to malignant hyperthermia due to volatile anesthetics and ex vivo assays demonstrate increased sensitivity to RYR1 agonists for knock-in myotubes, PS3 (PMID:30236258). This variant resides in a region of RYR1 considered to be a hotspot for pathogenic variants that contribute to MHS, PM1 (PMID: 21118704). This variant segregates with MHS in at least 20 individuals, PP1_Strong (PMID: 7849712, 11575529, 12059893, 25960145). A REVEL score >0.85 (0.956) supports a pathogenic status for this variant, PP3_Moderate. Based on using Bayes to combine criteria this variant is assessed as Pathogenic, (PMID: 29300386). Criteria implemented: PS3, PS4, PM1, PP1_Strong, PP3_Moderate, BS2. (less)
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Pathogenic
(Feb 08, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000852763.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 |
|
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Pathogenic
(Dec 10, 2019)
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criteria provided, single submitter
Method: clinical testing
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Malignant hyperthermia, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001429341.1
First in ClinVar: Aug 15, 2020 Last updated: Aug 15, 2020 |
Number of individuals with the variant: 1
|
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Pathogenic
(Aug 06, 2021)
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criteria provided, single submitter
Method: clinical testing
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Malignant hyperthermia susceptibility
Affected status: no
Allele origin:
germline
|
National Institute of Allergy and Infectious Diseases - Centralized Sequencing Program, National Institutes of Health
Accession: SCV002522194.2
First in ClinVar: Jun 05, 2022 Last updated: Oct 07, 2023 |
|
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Pathogenic
(Jan 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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Central core myopathy
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004175675.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
Comment:
The RYR1 c.7300G>A variant is classified as Pathogenic (PS3, PS4, PP3, PP5) The RYR1 c.7300G>A variant is a single nucleotide change in exon 45/106 of … (more)
The RYR1 c.7300G>A variant is classified as Pathogenic (PS3, PS4, PP3, PP5) The RYR1 c.7300G>A variant is a single nucleotide change in exon 45/106 of the RYR1 gene, which is predicted to change the amino acid glycine at position 2434 in the protein to arginine. The variant has been frequently reported in the literature in association with a malignant hyperthermia and central core disease (PS4). This variant is present at low frequency in population databases. Lopez et al (2018) reports that RYR1 p.G2435R knock-in mice demonstrated gene dose-dependent in vitro and in vivo responses to pharmacological and environmental stressors that parallel those seen in patients with the human RYR1 variant p.G2434R (PMID: 30236258) (PS3). Computational predictions support a deleterious effect on the gene or gene product (PP3). The variant has been reported in dbSNP (rs121918593) and in the HGMD database: CM941269. It has been reported as Drug response by other diagnostic laboratories (ClinVar Variation ID: 12970), including the ClinGen Malignant Hyperthermia Susceptibility Variant Curation Expert Panel (PP5). (less)
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Pathogenic
(Dec 10, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002019949.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
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Pathogenic
(Mar 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
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Malignant hyperthermia, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV004358126.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces glycine with arginine at codon 2434 of the RYR1 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces glycine with arginine at codon 2434 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). A study using genetically engineered mice has shown that mice carrying this variant develop malignant hyperthermia when exposed to halothane (PMID: 30236258). Further, functional studies on myotubes from the genetically engineered mice showed increased sensitivity to caffeine, halothane, and KCI in comparison to myotubes expressing wild-type RYR1 (PMID: 30236258). This variant has been reported in over 100 families and individuals affected with malignant hyperthermia susceptibility (PMID: 21455645, 23558838, 23842196, 24433488, 25268394, 25735680, 25960145, 27646467, 30236257, 30788618, 31206373). This variant has been identified in 11/282648 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Feb 05, 2024)
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criteria provided, single submitter
Method: clinical testing
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Malignant hyperthermia of anesthesia
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Molecular Genetics, Royal Melbourne Hospital
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002503670.2
First in ClinVar: Apr 30, 2022 Last updated: Apr 15, 2024 |
Comment:
This sequence change in RYR1 is predicted to replace glycine with arginine at codon 2434, p.(Gly2434Arg). The glycine residue is highly conserved (100 vertebrates, Multiz … (more)
This sequence change in RYR1 is predicted to replace glycine with arginine at codon 2434, p.(Gly2434Arg). The glycine residue is highly conserved (100 vertebrates, Multiz Alignments), and is located in exon 45 in the central region, amino acids 2,101-2,458, which is defined as a mutational hotspot. There is a large physicochemical difference between glycine and arginine. The highest population minor allele frequency in the population database gnomAD v4.0 is 0.01% (149/1,180,014 alleles) in the European (non-Finnish) population. The variant is the most common malignant hyperthermia susceptibility (MHS) variant detected in the United Kingdom (PMID: 30236257), and segregates with MHS in multiple families (PMID: 7849712). In vitro functional studies are supportive of a gain of function effect on intracellular calcium release and a knock-in mouse model recapitulates the human MHS response (PMID: 9334205, 27586648, 30236258). Computational evidence predicts a deleterious effect for the missense substitution (REVEL = 0.965). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as PATHOGENIC. Following criteria are met: PM1, PP1_Strong, PP3_Moderate, PS3, PS4. (less)
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Pathogenic
(Jan 15, 2020)
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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: SCV000711729.3
First in ClinVar: Apr 09, 2018 Last updated: Apr 20, 2024 |
Comment:
The p.Gly2434Arg variant in RYR1 is an established pathogenic variant for malignant hyperthermia (MH). It has been reported in >100 individuals with MH and segregated … (more)
The p.Gly2434Arg variant in RYR1 is an established pathogenic variant for malignant hyperthermia (MH). It has been reported in >100 individuals with MH and segregated with disease in >100 affected relatives from several families (Keating 1994, Phillips 1994, Richter 1997, Sambuughin 2001, Carpenter 2009, Dlamini 2013). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID 12970) and has been identified in 0.008% (10/129020) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This frequency is low enough to be consistent with the frequency of MH in the general population. In-vitro functional studies provide evidence that the p.Gly2434Arg variant may impact protein function (Richter 1997, Tong 1999, Girard 2001, Weigl 2004). In summary, this variant meets criteria to be classified as pathogenic for MH in an autosomal dominant manner. ACMG/AMP Criteria applied: PS4, PP1_Strong, PS3_Moderate. (less)
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Pathogenic
(Sep 30, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV003575370.2
First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024 |
Comment:
The c.7300G>A (p.G2434R) alteration is located in exon 45 (coding exon 45) of the RYR1 gene. This alteration results from a G to A substitution … (more)
The c.7300G>A (p.G2434R) alteration is located in exon 45 (coding exon 45) of the RYR1 gene. This alteration results from a G to A substitution at nucleotide position 7300, causing the glycine (G) at amino acid position 2434 to be replaced by an arginine (R). Based on data from gnomAD, the A allele has an overall frequency of 0.004% (11/282,648) total alleles studied. The highest observed frequency was 0.008% (10/129,020) of European (non-Finnish) alleles. This alteration has been reported heterozygous in multiple patients and their family members with features consistent with malignant hyperthermia (Keating, 1994; Riazi, 2014; Snoeck, 2015; Witting, 2018; Knuiman, 2019). This amino acid position is highly conserved in available vertebrate species. This alteration has been shown in vitro to enhance the sensitivity of RYR1 to activating concentrations of Ca2+ and to the exogenous ligands, caffeine and 4-chloro-m-cresol. The study also showed reduced sensitivity to inhibiting concentrations of Ca2+ and calmodulin, transferring the mutant Ca2+ release channel into a hyperexcitable state (Richter, 1997). Another study by Chen et al. (2017) showed that the p.G2434R alteration, when expressed in HEK293 cells, reduced the threshold for store overload-induced Ca2+ release (SOICR), allowing for spontaneous Ca2+ release from the sarcoplasmic reticulum, which has been proposed as the cause of uncontrolled muscle contraction. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. (less)
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Pathogenic
(Mar 01, 2023)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001249988.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Comment:
RYR1: PP1:Strong, PS3, PS4, PM1, PP3, BS2
Number of individuals with the variant: 9
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Pathogenic
(Nov 23, 2016)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000490785.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 |
Comment:
The G2434R variant in the RYR1 gene has been published previously as a pathogenic variant associated with malignant hyperthermia (Keating et al., 1994; Carpenter et … (more)
The G2434R variant in the RYR1 gene has been published previously as a pathogenic variant associated with malignant hyperthermia (Keating et al., 1994; Carpenter et al., 2009; Riazi et al., 2014). The G2434R variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G2434R variant is a non-conservative amino acid substitution, which occurs at a position that is conserved across species. Based on the ACMG recommendations, G2434R is interpreted as a pathogenic variant. (less)
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Pathogenic
(May 25, 2017)
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criteria provided, single submitter
Method: clinical testing
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Malignant hyperthermia, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV000840061.1
First in ClinVar: Oct 13, 2018 Last updated: Oct 13, 2018 |
Comment:
This c.7300G>A (p.Gly2434Arg) variant in the RYR1 gene has previously been reported in multiple patients with malignant hyperthermia [PMID 7849712, 23842196, 19648156, 11668625]. This variant … (more)
This c.7300G>A (p.Gly2434Arg) variant in the RYR1 gene has previously been reported in multiple patients with malignant hyperthermia [PMID 7849712, 23842196, 19648156, 11668625]. This variant has been functionally characterized and shown to have an increased sensitivity to activating concentrations of Ca2+ and to caffeine and 4-chloro-m-cresol in vitro. The variant is classified as pathogenic by the European malignant hyperthermia group (https://emhg.org). This variant has been observed in one 3 heterozygous individual from the ExAC database (http://exac.broadinstitute.org/variant/19-38990633-G-A). Glycine at position 2434 of the RYR1 protein is highly conserved. While not clinically validated, computer-based algorithms SIFT and Polyphen2 predict this p.Gly2434Arg change to be deleterious. It is thus interpreted as a pathogenic variant. (less)
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Pathogenic
(Feb 28, 2020)
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criteria provided, single submitter
Method: research
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Malignant hyperthermia, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
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HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Study: AGHI_GT
Accession: SCV000778611.2 First in ClinVar: Sep 04, 2016 Last updated: Jul 19, 2020 |
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 1
Observation 3:
Number of individuals with the variant: 1
Observation 4:
Number of individuals with the variant: 1
Observation 5:
Number of individuals with the variant: 1
Observation 6:
Number of individuals with the variant: 1
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal unknown)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447354.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Myopathy (present)
Sex: female
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Pathogenic
(Aug 25, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV001468077.1
First in ClinVar: Jan 05, 2021 Last updated: Jan 05, 2021 |
Comment on evidence:
PS3, PS4, PP1, PP3, PM1
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Pathogenic
(Sep 24, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics
Accession: SCV001880064.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant is also referred to as p.Gly2433Arg and p.Gly2435Arg in … (more)
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant is also referred to as p.Gly2433Arg and p.Gly2435Arg in some published literature. Computational tools yielded predictions that this variant may result in the gain of a cryptic splice site without affecting the natural splice sites. This variant segregates with disease in multiple families with susceptibility to malignant hyperthermia. Assessment of experimental evidence suggests this variant results in abnormal protein function. This variant leads to impaired calcium homeostasis (PMID: 9334205, 30236258, 27586648). Computational tools predict that this variant is damaging. (less)
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Pathogenic
(Jan 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: yes
Allele origin:
germline
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AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002501735.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Secondary finding: no
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Pathogenic
(May 30, 2022)
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criteria provided, single submitter
Method: clinical testing
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Central core myopathy
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002580012.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PS3, PP1_STR, PM1, PM2_SUP, PP3, PP4
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Number of individuals with the variant: 3
Sex: female
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Pathogenic
(Jan 24, 2024)
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criteria provided, single submitter
Method: clinical testing
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RYR1-related disorder
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000660024.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2434 of the RYR1 protein (p.Gly2434Arg). … (more)
This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2434 of the RYR1 protein (p.Gly2434Arg). This variant is present in population databases (rs121918593, gnomAD 0.008%). This missense change has been observed in individuals with malignant hyperthermia (PMID: 7849712, 9030597, 10484775, 11668625, 19648156, 23842196, 24433488). It has also been observed to segregate with disease in related individuals. This variant is also known as p.Gly2433Arg. ClinVar contains an entry for this variant (Variation ID: 12970). 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) performed at Invitae indicates that this missense variant is expected to disrupt RYR1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects RYR1 function (PMID: 9030597, 9334205). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 08, 2024)
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criteria provided, single submitter
Method: clinical testing
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Malignant hyperthermia, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004820910.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
The c.7300G>A (p.Gly2434Arg) variant, located on the exon 45 of the RYR1 gene, replaces glycine with arginine at codon 2434 of the RYR1 protein (p.Gly2434Arg). … (more)
The c.7300G>A (p.Gly2434Arg) variant, located on the exon 45 of the RYR1 gene, replaces glycine with arginine at codon 2434 of the RYR1 protein (p.Gly2434Arg). This missense change has been observed in >100 individuals with personal or family histories of a malignant hyperthermia reaction, positive in vitro contracture test (IVCT) or caffeine halothane contracture test (CHCT) (PMID: 30236257, 10484775, 23558838, 16163667, 21455645, 23842196, 7849712, 7881417, 11575529, 15731587, 11668625, 12059893, 12151923, 31559918, 10700782, 17081125, 18564801, 20681998, 21965348, 23460944, 25735680, 25960145, 9030597, 25268394, 17667681). This variant segregates with malignant hyperthermia (MHS) in at least 20 individuals (PMID: 7849712, 11575529, 12059893, 25960145). This missense variant is located in a mutational hot spot region that contributes to MHS (PMID: 21118704). A functional study in HEK293 cells shows an increased sensitivity to RYR1 agonists (PMID: 27586648). Such effect was confirmed in human skeletal muscle specimens isolated from MHS individuals carrying this RYR1 variant (PMID:9030597). Additionally, p.Gly2434Arg knock-in mice are susceptible to malignant hyperthermia due to volatile anesthetics, and ex vivo assays demonstrate increased sensitivity to RYR1 agonists for knock-in myotubes (PMID:30236258). Computational prediction (REVEL >0.85) suggests that this variant may have deleterious impact on protein structure and function. For these reasons, the c.7300G>A (p.Gly2434Arg) variant of RYR1 is classified as pathogenic. (less)
Number of individuals with the variant: 9
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Pathogenic
(Sep 16, 2018)
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no assertion criteria provided
Method: research
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not provided
Affected status: yes
Allele origin:
germline
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Gharavi Laboratory, Columbia University
Accession: SCV000809466.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 |
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risk factor
(Feb 21, 1997)
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no assertion criteria provided
Method: literature only
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MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000034084.4
First in ClinVar: Apr 04, 2013 Last updated: Oct 02, 2021 |
Comment on evidence:
In 4 of 104 unrelated families with MHS (145600), Keating et al. (1994) identified a gly2433-to-arg (GLY2433ARG) change in the RYR1 gene. The authors noted … (more)
In 4 of 104 unrelated families with MHS (145600), Keating et al. (1994) identified a gly2433-to-arg (GLY2433ARG) change in the RYR1 gene. The authors noted that this mutation is adjacent to the R2434H mutation (180901.0003), which may indicate a second cluster in the RYR1 gene where MHS and/or central core disease (117000) mutations occur. In the numbering system of amino acids provided by the corrected sequence data for human RYR1 according to Phillips et al. (1996), this mutation was referred to as G2434R by Richter et al. (1997). Functional studies showed that the G2434R mutation enhanced the sensitivity of RYR1 to activating concentrations of calcium and to caffeine. In parallel, the sensitivity to inhibiting concentrations of calcium and calmodulin was reduced, transferring the mutant calcium- release channel into a hyperexcitable state. (less)
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Pathogenic
(Sep 02, 2016)
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no assertion criteria provided
Method: provider interpretation
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not provided
Affected status: unknown
Allele origin:
germline
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Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000925213.1
First in ClinVar: Jul 01, 2019 Last updated: Jul 01, 2019 |
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not provided
(-)
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no classification provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
unknown
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Leiden Muscular Dystrophy (RYR1)
Accession: SCV000154605.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 |
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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 |
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Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. | Capalbo A | PLoS genetics | 2019 | PMID: 31589614 |
Bayesian modeling to predict malignant hyperthermia susceptibility and pathogenicity of RYR1, CACNA1S and STAC3 variants. | Sadhasivam S | Pharmacogenomics | 2019 | PMID: 31559918 |
Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network. | eMERGE Consortium. Electronic address: agibbs@bcm.edu | American journal of human genetics | 2019 | PMID: 31447099 |
Congenital myopathies in the adult neuromuscular clinic: Diagnostic challenges and pitfalls. | Nicolau S | Neurology. Genetics | 2019 | PMID: 31321302 |
An Assessment of Penetrance and Clinical Expression of Malignant Hyperthermia in Individuals Carrying Diagnostic Ryanodine Receptor 1 Gene Mutations. | Ibarra Moreno CA | Anesthesiology | 2019 | PMID: 31206373 |
The histopathological spectrum of malignant hyperthermia and rhabdomyolysis due to RYR1 mutations. | Knuiman GJ | Journal of neurology | 2019 | PMID: 30788618 |
Malignant hyperthermia, environmental heat stress, and intracellular calcium dysregulation in a mouse model expressing the p.G2435R variant of RYR1. | Lopez JR | British journal of anaesthesia | 2018 | PMID: 30236258 |
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 |
Reduced threshold for store overload-induced Ca(2+) release is a common defect of RyR1 mutations associated with malignant hyperthermia and central core disease. | Chen W | The Biochemical journal | 2017 | PMID: 28687594 |
Malignant hyperthermia susceptibility in patients with exertional rhabdomyolysis: a retrospective cohort study and updated systematic review. | Kraeva N | Canadian journal of anaesthesia = Journal canadien d'anesthesie | 2017 | PMID: 28326467 |
Muscular body build and male sex are independently associated with malignant hyperthermia susceptibility. | Butala B | Canadian journal of anaesthesia = Journal canadien d'anesthesie | 2017 | PMID: 28063098 |
Aggregate penetrance of genomic variants for actionable disorders in European and African Americans. | Natarajan P | Science translational medicine | 2016 | PMID: 27831900 |
Hypermetabolism in B-lymphocytes from malignant hyperthermia susceptible individuals. | Hoppe K | Scientific reports | 2016 | PMID: 27646467 |
Genotype-Phenotype Correlations of Malignant Hyperthermia and Central Core Disease Mutations in the Central Region of the RYR1 Channel. | Murayama T | Human mutation | 2016 | PMID: 27586648 |
Dantrolene as a possible prophylactic treatment for RYR1-related rhabdomyolysis. | Scalco RS | European journal of neurology | 2016 | PMID: 27431030 |
Identification of variants of the ryanodine receptor type 1 in patients with exertional heat stroke and positive response to the malignant hyperthermia in vitro contracture test. | Roux-Buisson N | British journal of anaesthesia | 2016 | PMID: 26994242 |
RYR1-related myopathies: a wide spectrum of phenotypes throughout life. | Snoeck M | European journal of neurology | 2015 | PMID: 25960145 |
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 |
Malignant hyperthermia deaths related to inadequate temperature monitoring, 2007-2012: a report from the North American malignant hyperthermia registry of the malignant hyperthermia association of the United States. | Larach MG | Anesthesia and analgesia | 2014 | PMID: 25268394 |
Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study. | Klingler W | Orphanet journal of rare diseases | 2014 | PMID: 24433488 |
Malignant hyperthermia in Canada: characteristics of index anesthetics in 129 malignant hyperthermia susceptible probands. | Riazi S | Anesthesia and analgesia | 2014 | PMID: 23842196 |
Mutations in RYR1 are a common cause of exertional myalgia and rhabdomyolysis. | Dlamini N | Neuromuscular disorders : NMD | 2013 | PMID: 23628358 |
Ryanodine receptor type 1 gene variants in the malignant hyperthermia-susceptible population of the United States. | Brandom BW | Anesthesia and analgesia | 2013 | PMID: 23558838 |
CASQ1 gene is an unlikely candidate for malignant hyperthermia susceptibility in the North American population. | Kraeva N | Anesthesiology | 2013 | PMID: 23460944 |
Screening of the ryanodine 1 gene for malignant hyperthermia causative mutations by high resolution melt curve analysis. | Broman M | Anesthesia and analgesia | 2011 | PMID: 21965348 |
Ryanodine receptor type 1 gene mutations found in the Canadian malignant hyperthermia population. | Kraeva N | Canadian journal of anaesthesia = Journal canadien d'anesthesie | 2011 | PMID: 21455645 |
Mechanistic models for muscle diseases and disorders originating in the sarcoplasmic reticulum. | Maclennan DH | Biochimica et biophysica acta | 2011 | PMID: 21118704 |
Novel missense mutations and unexpected multiple changes of RYR1 gene in 75 malignant hyperthermia families. | Tammaro A | Clinical genetics | 2011 | PMID: 20681998 |
Genetic variation in RYR1 and malignant hyperthermia phenotypes. | Carpenter D | British journal of anaesthesia | 2009 | PMID: 19648156 |
Analysis of RYR1 haplotype profile in patients with malignant hyperthermia. | Carpenter D | Annals of human genetics | 2009 | PMID: 18945287 |
Identification of genetic mutations in Australian malignant hyperthermia families using sequencing of RYR1 hotspots. | Gillies RL | Anaesthesia and intensive care | 2008 | PMID: 18564801 |
Molecular genetic testing to diagnose malignant hyperthermia susceptibility. | Girard T | Journal of clinical anesthesia | 2008 | PMID: 18502356 |
The cause of the difference in the submental region: aberrant muscle bundles of the anterior belly of the digastric muscle. | Ozgur Z | The Journal of craniofacial surgery | 2007 | PMID: 17667681 |
Malignant hyperthermia and central core disease causative mutations in Swedish patients. | Broman M | Acta anaesthesiologica Scandinavica | 2007 | PMID: 17081152 |
Specificity of human cathepsin S determined by processing of peptide substrates and MHC class II-associated invariant chain. | Rückrich T | Biological chemistry | 2006 | PMID: 17081125 |
Mutations in RYR1 in malignant hyperthermia and central core disease. | Robinson R | Human mutation | 2006 | PMID: 16917943 |
Frequency and localization of mutations in the 106 exons of the RYR1 gene in 50 individuals with malignant hyperthermia. | Galli L | Human mutation | 2006 | PMID: 16835904 |
Perinatal diagnosis of malignant hyperthermia susceptibility. | Girard T | Anesthesiology | 2006 | PMID: 16732128 |
Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility. | Monnier N | Human mutation | 2005 | PMID: 16163667 |
Screening of the entire ryanodine receptor type 1 coding region for sequence variants associated with malignant hyperthermia susceptibility in the north american population. | Sambuughin N | Anesthesiology | 2005 | PMID: 15731587 |
Malignant hyperthermia in North America: genetic screening of the three hot spots in the type I ryanodine receptor gene. | Sei Y | Anesthesiology | 2004 | PMID: 15448513 |
4-chloro-m-cresol cannot detect malignant hyperthermia equivocal cells in an alternative minimally invasive diagnostic test of malignant hyperthermia susceptibility. | Weigl LG | Anesthesia and analgesia | 2004 | PMID: 15281512 |
Patients with malignant hyperthermia demonstrate an altered calcium control mechanism in B lymphocytes. | Sei Y | Anesthesiology | 2002 | PMID: 12411786 |
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 |
Results of contracture tests with halothane, caffeine, and ryanodine depend on different malignant hyperthermia-associated ryanodine receptor gene mutations. | Fiege M | Anesthesiology | 2002 | PMID: 12151923 |
RYR1 mutations causing central core disease are associated with more severe malignant hyperthermia in vitro contracture test phenotypes. | Robinson RL | Human mutation | 2002 | PMID: 12124989 |
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 |
Genotype-phenotype comparison of the Swiss malignant hyperthermia population. | Girard T | Human mutation | 2001 | PMID: 11668625 |
North American malignant hyperthermia population: screening of the ryanodine receptor gene and identification of novel mutations. | Sambuughin N | Anesthesiology | 2001 | PMID: 11575529 |
[Preliminary report: first identification of known mutation in the ryanodine receptor gene in a Japanese malignant hyperthermia pedigree]. | Ichihara Y | Masui. The Japanese journal of anesthesiology | 2000 | PMID: 10793526 |
Malignant hyperthermia causing Gly2435Arg mutation of the ryanodine receptor facilitates ryanodine-induced calcium release in myotubes. | Brinkmeier H | British journal of anaesthesia | 1999 | PMID: 10700782 |
Screening of the ryanodine receptor gene in 105 malignant hyperthermia families: novel mutations and concordance with the in vitro contracture test. | Brandt A | Human molecular genetics | 1999 | PMID: 10484775 |
Mutation screening of the RYR1 gene and identification of two novel mutations in Italian malignant hyperthermia families. | Barone V | Journal of medical genetics | 1999 | PMID: 10051009 |
Measurement of resting cytosolic Ca2+ concentrations and Ca2+ store size in HEK-293 cells transfected with malignant hyperthermia or central core disease mutant Ca2+ release channels. | Tong J | The Journal of biological chemistry | 1999 | PMID: 9873004 |
Caffeine and halothane sensitivity of intracellular Ca2+ release is altered by 15 calcium release channel (ryanodine receptor) mutations associated with malignant hyperthermia and/or central core disease. | Tong J | The Journal of biological chemistry | 1997 | PMID: 9334205 |
Functional characterization of a distinct ryanodine receptor mutation in human malignant hyperthermia-susceptible muscle. | Richter M | The Journal of biological chemistry | 1997 | PMID: 9030597 |
The structural organization of the human skeletal muscle ryanodine receptor (RYR1) gene. | Phillips MS | Genomics | 1996 | PMID: 8661021 |
The substitution of Arg for Gly2433 in the human skeletal muscle ryanodine receptor is associated with malignant hyperthermia. | Phillips MS | Human molecular genetics | 1994 | PMID: 7881417 |
Detection of a novel RYR1 mutation in four malignant hyperthermia pedigrees. | Keating KE | Human molecular genetics | 1994 | PMID: 7849712 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/1436fa1b-2178-480a-9711-337815571f93 | - | - | - | - |
https://www.pharmgkb.org/clinicalAnnotation/1183705812 | - | - | - | - |
https://www.pharmgkb.org/variant/PA166155544 | - | - | - | - |
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Text-mined citations for rs121918593 ...
HelpRecord last updated May 27, 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.