NM_000334.4(SCN4A):c.3811A>G (p.Met1271Val) AND Familial hyperkalemic periodic paralysis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 25, 2021
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:: RCV001899921.8

Allele description [Variation Report for NM_000334.4(SCN4A):c.3811A>G (p.Met1271Val)]

NM_000334.4(SCN4A):c.3811A>G (p.Met1271Val)

Genes:

GH-LCR:growth hormone locus control region [Gene]
SCN4A:sodium voltage-gated channel alpha subunit 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q23.3

Genomic location:

Preferred name:

NM_000334.4(SCN4A):c.3811A>G (p.Met1271Val)

HGVS:

NC_000017.11:g.63944774T>C
NG_011699.1:g.33145A>G
NG_042788.1:g.27682T>C
NM_000334.4:c.3811A>GMANE SELECT
NP_000325.4:p.Met1271Val
NC_000017.10:g.62022134T>C

Protein change:

M1271V

Links:

dbSNP: rs2144778458

NCBI 1000 Genomes Browser:

rs2144778458

Molecular consequence:

NM_000334.4:c.3811A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial hyperkalemic periodic paralysis
Synonyms:: Hyperkalemic periodic paralysis; Gamstorp episodic adynamy; Gamstorp disease
Identifiers:: MONDO: MONDO:0008224; MedGen: C0238357; Orphanet: 682; OMIM: 170500; Human Phenotype Ontology: HP:0007215

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002126328	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 25, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002126328

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 25, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, SCV002126328.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant has not been reported in the literature in individuals with SCN4A-related conditions. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with valine at codon 1271 of the SCN4A protein (p.Met1271Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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