NM_000334.4(SCN4A):c.5285G>A (p.Gly1762Glu) AND Familial hyperkalemic periodic paralysis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 9, 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:: RCV002225197.4

Allele description [Variation Report for NM_000334.4(SCN4A):c.5285G>A (p.Gly1762Glu)]

NM_000334.4(SCN4A):c.5285G>A (p.Gly1762Glu)

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.5285G>A (p.Gly1762Glu)

HGVS:

NC_000017.11:g.63940997C>T
NG_011699.1:g.36922G>A
NG_042788.1:g.23905C>T
NM_000334.4:c.5285G>AMANE SELECT
NP_000325.4:p.Gly1762Glu
NC_000017.10:g.62018357C>T

Protein change:

G1762E

Links:

dbSNP: rs1328990008

NCBI 1000 Genomes Browser:

rs1328990008

Molecular consequence:

NM_000334.4:c.5285G>A - 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
SCV002503748	Molecular Genetics, Royal Melbourne Hospital See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 9, 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

SCV002503748

Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 9, 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

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 Molecular Genetics, Royal Melbourne Hospital, SCV002503748.2

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

Description

This sequence change is predicted to replace glycine with glutamic acid at codon 1762 of the SCN4A protein (p.(Gly1762Glu)). The glycine residue is weakly conserved (100 vertebrates, UCSC), and is located in the cytoplasmic region in no known functional domain. There is a moderate physicochemical difference between glycine and glutamic acid. The variant is present in a single individual in a large population cohort (absent in gnomAD v2.1 and 1/152,192 alleles in gnomAD v3.1), and has not been reported in the relevant medical literature and databases. Multiple lines of computational evidence predict a benign effect for the missense substitution (5/6 algorithms). Based on the classification scheme RMH Modified ACMG Guidelines v1.3.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2_Supporting.

#	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 16, 2024

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