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NM_000069.3(CACNA1S):c.3437T>A (p.Met1146Lys) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 25, 2018
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:
RCV000699953.6

Allele description

NM_000069.3(CACNA1S):c.3437T>A (p.Met1146Lys)

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.3437T>A (p.Met1146Lys)
HGVS:
  • NC_000001.11:g.201059277A>T
  • NG_009816.2:g.58290T>A
  • NM_000069.3:c.3437T>AMANE SELECT
  • NP_000060.2:p.Met1146Lys
  • NC_000001.10:g.201028405A>T
  • NG_009816.1:g.58290T>A
  • NM_000069.2:c.3437T>A
Protein change:
M1146K
Links:
dbSNP: rs763707356
NCBI 1000 Genomes Browser:
rs763707356
Molecular consequence:
  • NM_000069.3:c.3437T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypokalemic periodic paralysis, type 1
Synonyms:
HypoPP
Identifiers:
MONDO: MONDO:0042979; MedGen: C3714580; Orphanet: 681; OMIM: 170400
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
SCV000828686Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jun 25, 2018) 		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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000828686.4

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

Description

This sequence change replaces methionine with lysine at codon 1146 of the CACNA1S protein (p.Met1146Lys). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and lysine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CACNA1S-related disease. This variant is present in population databases (rs763707356, ExAC 0.003%).

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

Last Updated: Jul 29, 2024