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NM_000069.3(CACNA1S):c.2690G>A (p.Arg897Lys) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 19, 2022
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:
RCV000545029.6

Allele description

NM_000069.3(CACNA1S):c.2690G>A (p.Arg897Lys)

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.2690G>A (p.Arg897Lys)
HGVS:
  • NC_000001.11:g.201066284C>T
  • NG_009816.2:g.51283G>A
  • NM_000069.3:c.2690G>AMANE SELECT
  • NP_000060.2:p.Arg897Lys
  • NC_000001.10:g.201035412C>T
  • NG_009816.1:g.51283G>A
  • NM_000069.2:c.2690G>A
Protein change:
R897K
Links:
dbSNP: rs1287079817
NCBI 1000 Genomes Browser:
rs1287079817
Molecular consequence:
  • NM_000069.3:c.2690G>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
SCV000653678Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 19, 2022) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Early onset of hypokalaemic periodic paralysis caused by a novel mutation of the CACNA1S gene.

Chabrier S, Monnier N, Lunardi J.

J Med Genet. 2008 Oct;45(10):686-8. doi: 10.1136/jmg.2008.059766.

PubMed [citation]
PMID:
18835861

Exploring the utility of whole-exome sequencing as a diagnostic tool in a child with atypical episodic muscle weakness.

Hanchard NA, Murdock DR, Magoulas PL, Bainbridge M, Muzny D, Wu Y, Wang M, Lupski JR, Gibbs RA, Brown CW.

Clin Genet. 2013 May;83(5):457-461. doi: 10.1111/j.1399-0004.2012.01951.x. Epub 2012 Sep 11.

PubMed [citation]
PMID:
22901280
PMCID:
PMC3926310
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000653678.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg897 amino acid residue in CACNA1S. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18835861, 22901280). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects CACNA1S function (PMID: 33005891). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 473979). This missense change has been observed in individuals with autosomal dominant hypokalemic periodic paralysis (PMID: 33005891). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 897 of the CACNA1S protein (p.Arg897Lys).

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

Last Updated: Feb 28, 2024