ClinVar Genomic variation as it relates to human health
NM_000540.3(RYR1):c.487C>T (p.Arg163Cys)
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.487C>T (p.Arg163Cys)
Variation ID: 12967 Accession: VCV000012967.21
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 19q13.2 19: 38444211 (GRCh38) [ NCBI UCSC ] 19: 38934851 (GRCh37) [ NCBI UCSC ] 19: 43626691 (NCBI36) [ 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 Feb 14, 2024 Mar 29, 2022 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000540.3:c.487C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000531.2:p.Arg163Cys missense NM_001042723.2:c.487C>T NP_001036188.1:p.Arg163Cys missense NC_000019.10:g.38444211C>T NC_000019.9:g.38934851C>T NG_008866.1:g.15512C>T LRG_766:g.15512C>T LRG_766t1:c.487C>T LRG_766p1:p.Arg163Cys P21817:p.Arg163Cys - Protein change
- R163C
- Other names
- NM_000540.3(RYR1):c.487C>T
- Canonical SPDI
- NC_000019.10:38444210: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.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
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 |
7820 | 8103 |
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 (2) |
reviewed by expert panel
|
Mar 29, 2022 | RCV000013833.13 | |
Pathogenic (1) |
no assertion criteria provided
|
Jul 11, 2001 | RCV000013834.34 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Sep 10, 2023 | RCV000119625.19 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jan 8, 2024 | RCV000806352.12 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV001787402.9 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV001787707.9 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV001787709.9 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV001787710.9 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV001787706.9 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV001787711.9 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV001787708.9 | |
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. |
|
---|---|---|---|---|---|
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: SCV000925456.2
First in ClinVar: Jun 30, 2019 Last updated: Dec 12, 2021 |
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: SCV000925457.2
First in ClinVar: Jun 30, 2019 Last updated: Dec 12, 2021 |
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: SCV000925458.2
First in ClinVar: Jun 30, 2019 Last updated: Dec 12, 2021 |
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: SCV000925454.2
First in ClinVar: Jun 30, 2019 Last updated: Dec 12, 2021 |
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
|
enflurane response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV000925455.2
First in ClinVar: Jun 30, 2019 Last updated: Dec 12, 2021 |
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: SCV000925257.2
First in ClinVar: Jun 30, 2019 Last updated: Dec 12, 2021 |
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: SCV000925258.2
First in ClinVar: Jun 30, 2019 Last updated: Dec 12, 2021 |
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
(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: SCV002570136.1
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 163 of the RYR1 protein p.(Arg163Cys). This variant is not present in a large population databases (gnomAD). This variant has been reported in over 40 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 (PMID:30236257, PMID:12151923, PMID:16163667, PMID:8220423, PMID:11575529, PMID:12059893, PMID:23558838 and others). This variant has been identified in 1 individual with negative IVCT/CHCT results, BS2_Moderate (PMID:30236257). Functional studies in HEK293 cells show an increased sensitivity to RYR1 agonists. A knock-in mouse model supports pathogenicity of this variant demonstrating a malignant hyperthermia reaction in response to agonist, as well ex vivo studies show increased response to agonist with increased calcium release, PS3 (PMID:20461000, PMID:9334205, PMID:17122579). Another variant assessed as likely pathogenic occurs at this codon, p.(Arg163Leu), PM5_Supporting. 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). This variant segregates with MHS over seven individuals, PP1_Strong (PMID:30236257, PMID:12059893, PMID:7889656). A REVEL score > 0.85 (0.959) supports pathogenicity, PP3_Moderate. Based on using Bayes to combine criteria this variant is assessed as Pathogenic, (PMID: 29300386). Criteria implemented: PS4, PS3, PM1_Supporting, PM5_Supporting, PP1_Strong, PP3_Moderate, BS2_Moderate. (less)
|
|
Pathogenic
(Sep 10, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000567432.5
First in ClinVar: Jun 09, 2014 Last updated: Sep 22, 2023 |
Comment:
Published functional studies demonstrate a damaging effect as R163C results in hypersensitivity to halothane and increased calcium release (Censier et al., 1998; Chen et al., … (more)
Published functional studies demonstrate a damaging effect as R163C results in hypersensitivity to halothane and increased calcium release (Censier et al., 1998; Chen et al., 2017); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as p.R164C; This variant is associated with the following publications: (PMID: 19541610, 20461000, 21156754, 20479108, 17122579, 32826313, 23459219, 12732639, 11524458, 9873004, 9334205, 8592342, 12411788, 28687594, 7889656, 9502764, 30499100, 19648156, 8220423, 21965348, 30236257, 12124989, 35741838, 35428369, 32403337, 33767344) (less)
|
|
Pathogenic
(Nov 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000852652.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 |
|
|
Pathogenic
(Aug 30, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002048509.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
Comment:
The RYR1 c.487C>T; p.Arg163Cys variant (rs118192161) is reported in individuals with malignant hyperthermia (MH) and central core disease (CCD) and segregates with MH and CCD … (more)
The RYR1 c.487C>T; p.Arg163Cys variant (rs118192161) is reported in individuals with malignant hyperthermia (MH) and central core disease (CCD) and segregates with MH and CCD in several families (Carpenter 2009, O'Brien 1995, Quane 1993). The variant is listed in the ClinVar database (Variation ID: 12967) but is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The arginine at codon 163 is moderately conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.959). Additionally, experimental studies show that this variant alters protein function in vitro and in vivo, including in a mouse model of this variant (Avila 2001, Feng 2011, Tong 1997). Based on available information, this variant is considered to be pathogenic. References: Avila G and Dirksen RT. Functional effects of central core disease mutations in the cytoplasmic region of the skeletal muscle ryanodine receptor. J Gen Physiol. 2001 Sep;118(3):277-90. PMID: 11524458. Carpenter D et al. Genetic variation in RYR1 and malignant hyperthermia phenotypes. Br J Anaesth. 2009 Oct;103(4):538-48. PMID: 19648156. Feng W et al. Functional and biochemical properties of ryanodine receptor type 1 channels from heterozygous R163C malignant hyperthermia-susceptible mice. Mol Pharmacol. 2011 Mar;79(3):420-31. PMID: 21156754. O'Brien RO et al. Exclusion of defects in the skeletal muscle specific regions of the DHPR alpha 1 subunit as frequent causes of malignant hyperthermia. J Med Genet. 1995 Nov;32(11):913-4. PMID: 8592342. Quane KA et al. Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia. Nat Genet. 1993 Sep;5(1):51-5. PMID: 8220423. Tong J et al. 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. J Biol Chem. 1997 Oct 17;272(42):26332-9. PMID: 9334205. (less)
|
|
Pathogenic
(Jan 08, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
RYR1-Related Disorders
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000946344.4
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 163 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 163 of the RYR1 protein (p.Arg163Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant malignant hyperthermia (MH) and central core disease (CCD) (PMID: 8220423, 8592342, 19648156). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 12967). 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: 9334205, 11524458, 21156754). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Jul 11, 2001)
|
no assertion criteria provided
Method: literature only
|
CENTRAL CORE DISEASE
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000034081.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 04, 2016 |
Comment on evidence:
In affected members of 2 unrelated families with malignant hyperthermia susceptibility (145600), Quane et al. (1993) identified an arg163-to-cys (R163C) substitution in the RYR1 gene. … (more)
In affected members of 2 unrelated families with malignant hyperthermia susceptibility (145600), Quane et al. (1993) identified an arg163-to-cys (R163C) substitution in the RYR1 gene. In 1 of these families, some persons also had manifestations of central core disease (117000). O'Brien et al. (1995) reported a family in which 2 members diagnosed with MHS by means of the in vitro contracture test were found to be heterozygous for the R163C mutation, but 2 other members diagnosed with MHS on the same basis did not have the mutation. Reference was made to other families in which the major phenotype did not cosegregate with the arg614-to-cys (180901.0001) or the gly341-to-arg (180901.0006) mutations. Fagerlund et al. (1994, 1995) found the R163C mutation in 1 of 48 Danish families with MHS, but in none of 41 Swedish families. Tobin et al. (2001) identified the R163C mutation in a 12-year-old boy with MHS. The patient's father also carried the mutation. (less)
|
|
risk factor
(Jul 11, 2001)
|
no assertion criteria provided
Method: literature only
|
MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000034080.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 04, 2016 |
Comment on evidence:
In affected members of 2 unrelated families with malignant hyperthermia susceptibility (145600), Quane et al. (1993) identified an arg163-to-cys (R163C) substitution in the RYR1 gene. … (more)
In affected members of 2 unrelated families with malignant hyperthermia susceptibility (145600), Quane et al. (1993) identified an arg163-to-cys (R163C) substitution in the RYR1 gene. In 1 of these families, some persons also had manifestations of central core disease (117000). O'Brien et al. (1995) reported a family in which 2 members diagnosed with MHS by means of the in vitro contracture test were found to be heterozygous for the R163C mutation, but 2 other members diagnosed with MHS on the same basis did not have the mutation. Reference was made to other families in which the major phenotype did not cosegregate with the arg614-to-cys (180901.0001) or the gly341-to-arg (180901.0006) mutations. Fagerlund et al. (1994, 1995) found the R163C mutation in 1 of 48 Danish families with MHS, but in none of 41 Swedish families. Tobin et al. (2001) identified the R163C mutation in a 12-year-old boy with MHS. The patient's father also carried the mutation. (less)
|
|
not provided
(-)
|
no classification provided
Method: not provided
|
not provided
Affected status: not provided
Allele origin:
unknown
|
Leiden Muscular Dystrophy (RYR1)
Accession: SCV000154532.1
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 |
---|---|---|---|---|
Malignant hyperthermia, a Scandinavian update. | Broman M | Acta anaesthesiologica Scandinavica | 2015 | PMID: 25989378 |
Ryanodine receptor type 1 gene variants in the malignant hyperthermia-susceptible population of the United States. | Brandom BW | Anesthesia and analgesia | 2013 | PMID: 23558838 |
Nonspecific sarcolemmal cation channels are critical for the pathogenesis of malignant hyperthermia. | Eltit JM | FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 2013 | PMID: 23159934 |
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 |
Functional and biochemical properties of ryanodine receptor type 1 channels from heterozygous R163C malignant hyperthermia-susceptible mice. | Feng W | Molecular pharmacology | 2011 | PMID: 21156754 |
Genetic variation in RYR1 and malignant hyperthermia phenotypes. | Carpenter D | British journal of anaesthesia | 2009 | PMID: 19648156 |
Identification of genetic mutations in Australian malignant hyperthermia families using sequencing of RYR1 hotspots. | Gillies RL | Anaesthesia and intensive care | 2008 | PMID: 18564801 |
Pharmacologic and functional characterization of malignant hyperthermia in the R163C RyR1 knock-in mouse. | Yang T | Anesthesiology | 2006 | PMID: 17122579 |
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 |
Malignant hyperthermia in Japan: mutation screening of the entire ryanodine receptor type 1 gene coding region by direct sequencing. | Ibarra M CA | Anesthesiology | 2006 | PMID: 16732084 |
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 |
Presence of two different genetic traits in malignant hyperthermia families: implication for genetic analysis, diagnosis, and incidence of malignant hyperthermia susceptibility. | Monnier N | Anesthesiology | 2002 | PMID: 12411788 |
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 |
North American malignant hyperthermia population: screening of the ryanodine receptor gene and identification of novel mutations. | Sambuughin N | Anesthesiology | 2001 | PMID: 11575529 |
Functional effects of central core disease mutations in the cytoplasmic region of the skeletal muscle ryanodine receptor. | Avila G | The Journal of general physiology | 2001 | PMID: 11524458 |
Malignant hyperthermia and apparent heat stroke. | Tobin JR | JAMA | 2001 | PMID: 11448278 |
Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation. | Manning BM | American journal of human genetics | 1998 | PMID: 9497245 |
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 |
Exclusion of defects in the skeletal muscle specific regions of the DHPR alpha 1 subunit as frequent causes of malignant hyperthermia. | O'Brien RO | Journal of medical genetics | 1995 | PMID: 8592342 |
A search for three known RYR1 gene mutations in 41 Swedish families with predisposition to malignant hyperthermia. | Fagerlund TH | Clinical genetics | 1995 | PMID: 7586638 |
Genotype and phenotype relationships for mutations in the ryanodine receptor in patients referred for diagnosis of malignant hyperthermia. | Fletcher JE | British journal of anaesthesia | 1995 | PMID: 7547049 |
Search for three known mutations in the RYR1 gene in 48 Danish families with malignant hyperthermia. | Fagerlund T | Clinical genetics | 1994 | PMID: 7889656 |
Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia. | Quane KA | Nature genetics | 1993 | PMID: 8220423 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/b2c419cf-7cdb-484f-8504-880aa4d39370 | - | - | - | - |
https://www.pharmgkb.org/clinicalAnnotation/1183705759 | - | - | - | - |
https://www.pharmgkb.org/variant/PA166155532 | - | - | - | - |
click to load more click to collapse |
Text-mined citations for rs118192161 ...
HelpRecord last updated Mar 23, 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.