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NM_000069.3(CACNA1S):c.1669C>T (p.Arg557Cys) AND Malignant hyperthermia, susceptibility to, 5

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Dec 1, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003455268.3

Allele description [Variation Report for NM_000069.3(CACNA1S):c.1669C>T (p.Arg557Cys)]

NM_000069.3(CACNA1S):c.1669C>T (p.Arg557Cys)

Gene:
CACNA1S:calcium voltage-gated channel subunit alpha1 S [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q32.1
Genomic location:
Preferred name:
NM_000069.3(CACNA1S):c.1669C>T (p.Arg557Cys)
HGVS:
  • NC_000001.11:g.201077078G>A
  • NG_009816.2:g.40489C>T
  • NM_000069.3:c.1669C>TMANE SELECT
  • NP_000060.2:p.Arg557Cys
  • NC_000001.10:g.201046206G>A
  • NC_000001.10:g.201046206G>A
  • NG_009816.1:g.40489C>T
  • NM_000069.2:c.1669C>T
Protein change:
R557C
Links:
dbSNP: rs756612471
NCBI 1000 Genomes Browser:
rs756612471
Molecular consequence:
  • NM_000069.3:c.1669C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
20

Condition(s)

Name:
Malignant hyperthermia, susceptibility to, 5 (MHS5)
Synonyms:
Malignant hyperthermia susceptibility type 5; Malignant hyperpyrexia susceptibility type 5
Identifiers:
MONDO: MONDO:0011163; MedGen: C1866077; Orphanet: 423; OMIM: 601887

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004179027Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Apr 11, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004822285All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Dec 1, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown20not providednot provided108544not providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Genome-Nilou Lab, SCV004179027.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004822285.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided20not providednot providedclinical testing PubMed (1)

Description

This missense variant replaces arginine with cysteine at codon 557 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CACNA1S-related disorders in the literature. This variant has been identified in 16/282846 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided20not providednot providednot provided

Last Updated: Sep 29, 2024