NM_000334.4(SCN4A):c.5104GAG[1] (p.Glu1703del) AND Familial hyperkalemic periodic paralysis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 7, 2023
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:: RCV000688042.7

Allele description [Variation Report for NM_000334.4(SCN4A):c.5104GAG[1] (p.Glu1703del)]

NM_000334.4(SCN4A):c.5104GAG[1] (p.Glu1703del)

Genes:

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

Variant type:

Microsatellite

Cytogenetic location:

17q23.3

Genomic location:

Preferred name:

NM_000334.4(SCN4A):c.5104GAG[1] (p.Glu1703del)

HGVS:

NC_000017.11:g.63941174TCC[1]
NG_011699.1:g.36741GAG[1]
NG_042788.1:g.24082TCC[1]
NM_000334.4:c.5104GAG[1]MANE SELECT
NP_000325.4:p.Glu1703del
NC_000017.10:g.62018533_62018535del
NC_000017.10:g.62018534TCC[1]
NM_000334.4:c.5107_5109delGAGMANE SELECT

Protein change:

E1703del

Links:

dbSNP: rs1464481652

NCBI 1000 Genomes Browser:

rs1464481652

Molecular consequence:

NM_000334.4:c.5104GAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

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
SCV000815638	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 7, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32129495, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000815638

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 7, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

EF hand-like motif mutations of Nav1.4 C-terminus cause myotonic syndrome by impairing fast inactivation.

Horie R, Kubota T, Koh J, Tanaka R, Nakamura Y, Sasaki R, Ito H, Takahashi MP.

Muscle Nerve. 2020 Jun;61(6):808-814. doi: 10.1002/mus.26849. Epub 2020 Mar 17.

PubMed [citation]

PMID:: 32129495

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, SCV000815638.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant, c.5107_5109del, results in the deletion of 1 amino acid(s) of the SCN4A protein (p.Glu1703del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.003%). 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. Experimental studies have shown that this variant affects SCN4A function (PMID: 32129495). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 567853). This variant is also known as p.Glu1702del. This variant has been observed in individual(s) with SCN4A-related conditions (PMID: 32129495).

#	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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