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NM_000069.3(CACNA1S):c.4569C>G (p.Phe1523Leu) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 4, 2019
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:
RCV001047961.8

Allele description [Variation Report for NM_000069.3(CACNA1S):c.4569C>G (p.Phe1523Leu)]

NM_000069.3(CACNA1S):c.4569C>G (p.Phe1523Leu)

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.4569C>G (p.Phe1523Leu)
HGVS:
  • NC_000001.11:g.201047214G>C
  • NG_009816.2:g.70353C>G
  • NM_000069.3:c.4569C>GMANE SELECT
  • NP_000060.2:p.Phe1523Leu
  • NC_000001.10:g.201016342G>C
  • NG_009816.1:g.70353C>G
  • NM_000069.2:c.4569C>G
Protein change:
F1523L
Links:
dbSNP: rs995172326
NCBI 1000 Genomes Browser:
rs995172326
Molecular consequence:
  • NM_000069.3:c.4569C>G - 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
SCV001211947Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 4, 2019) 		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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001211947.5

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

Description

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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CACNA1S-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 1523 of the CACNA1S protein (p.Phe1523Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine.

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

Last Updated: Sep 29, 2024