ClinVar Genomic variation as it relates to human health
NM_000069.3(CACNA1S):c.520C>T (p.Arg174Trp)
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_000069.3(CACNA1S):c.520C>T (p.Arg174Trp)
Variation ID: 575733 Accession: VCV000575733.43
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q32.1 1: 201091993 (GRCh38) [ NCBI UCSC ] 1: 201061121 (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 Oct 10, 2018 Apr 20, 2024 Mar 24, 2021 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000069.3:c.520C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000060.2:p.Arg174Trp missense NC_000001.11:g.201091993G>A NC_000001.10:g.201061121G>A NG_009816.2:g.25574C>T - Protein change
- R174W
- Other names
- -
- Canonical SPDI
- NC_000001.11:201091992: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.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00003
- Links
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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CACNA1S | No evidence available | No evidence available |
GRCh38 GRCh37 |
2646 | 2676 |
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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Likely pathogenic (1) |
criteria provided, single submitter
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Jan 2, 2024 | RCV000698038.17 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 14, 2023 | RCV001093102.26 | |
Uncertain significance (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV001096586.12 | |
drug response (1) |
reviewed by expert panel
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Mar 24, 2021 | RCV001788330.9 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV001788336.9 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV001788331.9 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV001788332.9 | |
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV001788333.9 | |
drug response (1) |
reviewed by expert panel
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Mar 24, 2021 | RCV001788334.9 | |
drug response (1) |
reviewed by expert panel
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Mar 24, 2021 | RCV001788335.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 30, 2023 | RCV002249414.10 | |
Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2024 | RCV002468602.12 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jun 1, 2023 | RCV004017719.1 | |
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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
(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: SCV000925356.2
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)
|
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drug response
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
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enflurane response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV002031243.1
First in ClinVar: Dec 12, 2021 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)
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drug response
(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
|
PharmGKB
Accession: SCV002031244.1
First in ClinVar: Dec 12, 2021 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)
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drug response
(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: SCV002031245.1
First in ClinVar: Dec 12, 2021 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)
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drug response
(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: SCV002031246.1
First in ClinVar: Dec 12, 2021 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)
|
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drug response
(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: SCV002031247.1
First in ClinVar: Dec 12, 2021 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)
|
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drug response
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
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succinylcholine response - Toxicity
Drug used for
Malignant Hyperthermia
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV002031248.1
First in ClinVar: Dec 12, 2021 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)
|
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Uncertain significance
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hypokalemic periodic paralysis, type 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001252805.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Pathogenic
(Jun 17, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001762251.1
First in ClinVar: Jul 30, 2021 Last updated: Jul 30, 2021 |
Clinical Features:
Myotonia (present) , Myopathy (present)
Sex: male
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Pathogenic
(Nov 09, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Malignant hyperthermia, susceptibility to, 5
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV002764958.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Number of individuals with the variant: 1
Clinical Features:
Malignant hyperthermia (present) , Myopathy (present) , Exercise-induced muscle cramps (present)
|
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Pathogenic
(Mar 14, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001791847.2
First in ClinVar: Aug 18, 2021 Last updated: Apr 01, 2023 |
Comment:
Published functional studies demonstrate impaired Ca2+ depolarization and increased sensitivity of Ca2+ release to caffeine and volatile anesthetics (Bannister et al., 2013; Eltit et al., … (more)
Published functional studies demonstrate impaired Ca2+ depolarization and increased sensitivity of Ca2+ release to caffeine and volatile anesthetics (Bannister et al., 2013; Eltit et al., 2012), while R174W-expressing myotubes had elevated Ca2+ levels and sarcoplasmic reticulum stores were partially depleted (Eltit et al., 2012); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23663834, 22547813, 21664226, 19825159, 21845430, 24433488, 34426522, 30236257) (less)
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Pathogenic
(Mar 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
|
Mendelics
Accession: SCV002518021.2
First in ClinVar: May 28, 2022 Last updated: Apr 01, 2023 |
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Pathogenic
(Apr 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Malignant hyperthermia, susceptibility to, 5
Affected status: unknown
Allele origin:
germline
|
New York Genome Center
Accession: SCV004176081.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
Comment:
The c.520C>T variant in CACNA1S has previously been reported in individuals with malignant hyperthermia susceptibility [PMID: 19825159, 24433488, 30236257], and it has been deposited in … (more)
The c.520C>T variant in CACNA1S has previously been reported in individuals with malignant hyperthermia susceptibility [PMID: 19825159, 24433488, 30236257], and it has been deposited in ClinVar as Pathogenic by an expert panel (PharmGKB Expert Review Panel [ClinVar ID: 575733]). The c.520C>T variant is observed in 11 alleles (0.0018% minor allele frequency with 0 homozygotes) in population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases. The c.520C>T variant is located in exon 4 of this 44-exon gene and is predicted to replace an evolutionarily conserved arginine amino acid with tryptophan at position 174 (p.(Arg174Trp)) in the S4 helix of the first conserved membrane repeat of the encodedprotein that is known to be important in sensing changes in the membrane potential [PMID: 19825159, 23663834]. In vitro studies demonstrated elevated resting myoplasmic calcium levels and partially depleted sarcoplasmic reticulum stores in myoblast cells carrying the c.520C>T variant [PMID: 23663834, 22547813]. Basedon available evidence this heterozygous c.520C>T p.(Arg174Trp) variant identified in CACNA1S is classified as Pathogenic. (less)
Clinical Features:
Cardiomyopathy (present)
Secondary finding: yes
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Likely pathogenic
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Malignant hyperthermia, susceptibility to, 5
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004244364.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
Criteria applied: PS4,PS3_SUP,PM2_SUP,PP1,PP3
Clinical Features:
Malignant hyperthermia (present)
Sex: female
|
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Likely pathogenic
(Sep 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Malignant hyperthermia, susceptibility to, 5
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV004360411.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces arginine with tryptophan at codon 174 of the CACNA1S protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces arginine with tryptophan at codon 174 of the CACNA1S 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 functional study in myotubes showed that this variant increases sensitivity to isoflurane and halothane compared to wild-type protein (PMID: 22547813). This variant has been reported in at least six individuals affected with malignant hyperthermia susceptibility (PMID: 19825159, 24433488, 28259615, 30236257, 33564012, 33564012, DOI: 10.24811/hjms.71.1-2_31). In one family, this variant was observed in a proband and his mother affected with malignant hyperthermia susceptibility and was absent in his unaffected sibling (PMID: 19825159). This variant has been identified in 7/251362 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
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Likely pathogenic
(Jan 02, 2024)
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criteria provided, single submitter
Method: clinical testing
|
Hypokalemic periodic paralysis, type 1
Malignant hyperthermia, susceptibility to, 5
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000826678.7
First in ClinVar: Oct 10, 2018 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 174 of the CACNA1S protein … (more)
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 174 of the CACNA1S protein (p.Arg174Trp). This variant is present in population databases (rs772226819, gnomAD 0.01%). This missense change has been observed in individuals with autosomal dominant malignant hyperthermia susceptibility (PMID: 1982519, 24433488, 30236257). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 575733). 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 CACNA1S protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects CACNA1S function (PMID: 22547813, 23663834). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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Pathogenic
(Dec 01, 2021)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001249926.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 2
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Likely Pathogenic
(Aug 16, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Malignant hyperthermia, susceptibility to, 5
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004821967.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
This missense variant replaces arginine with tryptophan at codon 174 of the CACNA1S protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces arginine with tryptophan at codon 174 of the CACNA1S 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 functional study in myotubes showed that this variant increases sensitivity to isoflurane and halothane compared to wild-type CACNA1S (PMID: 22547813). This variant has been reported in at least six individuals affected with malignant hyperthermia susceptibility (PMID: 19825159, 24433488, 28259615, 30236257, 33564012, 33564012, DOI: 10.24811/hjms.71.1-2_31). It has been shown that this variant segregates with disease in at least one family (PMID: 33564012). This variant has been identified in 7/251362 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
Number of individuals with the variant: 4
|
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Likely Pathogenic
(Jun 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Malignant hyperthermia of anesthesia
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004848031.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
proposed classification - variant undergoing re-assessment, contact laboratory
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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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Relevance of pathogenicity prediction tools in human RYR1 variants of unknown significance. | Hoppe K | Scientific reports | 2021 | PMID: 33564012 |
Genetic epidemiology of malignant hyperthermia in the UK. | Miller DM | British journal of anaesthesia | 2018 | PMID: 30236257 |
Resequencing array for gene variant detection in malignant hyperthermia and butyrylcholinestherase deficiency. | Levano S | Neuromuscular disorders : NMD | 2017 | PMID: 28259615 |
Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study. | Klingler W | Orphanet journal of rare diseases | 2014 | PMID: 24433488 |
Impaired gating of an L-Type Ca(2+) channel carrying a mutation linked to malignant hyperthermia. | Bannister RA | Biophysical journal | 2013 | PMID: 23663834 |
Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca2+ channel and the type 1 ryanodine receptor. | Eltit JM | Proceedings of the National Academy of Sciences of the United States of America | 2012 | PMID: 22547813 |
The role of CACNA1S in predisposition to malignant hyperthermia. | Carpenter D | BMC medical genetics | 2009 | PMID: 19825159 |
HIV/AIDS management in Africa--new directions from the San Francisco Conference. | Campbell ID | AIDS care | 1990 | PMID: 1982519 |
https://www.pharmgkb.org/clinicalAnnotation/1449563861 | - | - | - | - |
https://www.pharmgkb.org/clinicalAnnotation/1451264060 | - | - | - | - |
https://www.pharmgkb.org/clinicalAnnotation/1451264081 | - | - | - | - |
https://www.pharmgkb.org/clinicalAnnotation/1451264087 | - | - | - | - |
https://www.pharmgkb.org/clinicalAnnotation/1451264120 | - | - | - | - |
https://www.pharmgkb.org/clinicalAnnotation/1451264128 | - | - | - | - |
https://www.pharmgkb.org/clinicalAnnotation/1451264140 | - | - | - | - |
https://www.pharmgkb.org/variant/PA166153940 | - | - | - | - |
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Text-mined citations for rs772226819 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.