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NM_000069.3(CACNA1S):c.1583G>T (p.Arg528Leu) AND Malignant hyperthermia, susceptibility to, 5

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 3, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003517221.1

Allele description [Variation Report for NM_000069.3(CACNA1S):c.1583G>T (p.Arg528Leu)]

NM_000069.3(CACNA1S):c.1583G>T (p.Arg528Leu)

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.1583G>T (p.Arg528Leu)
HGVS:
  • NC_000001.11:g.201077915C>A
  • NG_009816.2:g.39652G>T
  • NM_000069.3:c.1583G>TMANE SELECT
  • NP_000060.2:p.Arg528Leu
  • NC_000001.10:g.201047043C>A
  • NG_009816.1:g.39652G>T
  • NM_000069.2:c.1583G>T
Protein change:
R528L
Links:
dbSNP: rs80338777
NCBI 1000 Genomes Browser:
rs80338777
Molecular consequence:
  • NM_000069.3:c.1583G>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV004360382Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Feb 3, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot 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 Color Diagnostics, LLC DBA Color Health, SCV004360382.1

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

Description

This missense variant replaces arginine with leucine at codon 528 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 autosomal dominant malignant hyperthermia in the literature, although it is associated with other phenotypes (ClinVar Variation ID: 473965; PMID: 25430699, 29193480, 31321302). This variant has been identified in 3/251124 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Due to insufficient evidence, this variant is classified as a Variant of Uncertain Significance for autosomal dominant malignant hyperthermia.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 26, 2024