NM_000335.5(SCN5A):c.677C>A (p.Ala226Asp) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 24, 2020
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:: RCV003541330.1

Allele description [Variation Report for NM_000335.5(SCN5A):c.677C>A (p.Ala226Asp)]

NM_000335.5(SCN5A):c.677C>A (p.Ala226Asp)

Gene:

SCN5A:sodium voltage-gated channel alpha subunit 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000335.5(SCN5A):c.677C>A (p.Ala226Asp)

HGVS:

NC_000003.12:g.38613769G>T
NG_008934.1:g.40904C>A
NM_000335.5:c.677C>AMANE SELECT
NM_001099404.2:c.703+206C>A
NM_001099405.2:c.703+206C>A
NM_001160160.2:c.703+206C>A
NM_001160161.2:c.703+206C>A
NM_001354701.2:c.703+206C>A
NM_198056.3:c.677C>A
NP_000326.2:p.Ala226Asp
NP_932173.1:p.Ala226Asp
LRG_289:g.40904C>A
NC_000003.11:g.38655260G>T

Protein change:

A226D

Links:

dbSNP: rs199473561

NCBI 1000 Genomes Browser:

rs199473561

Molecular consequence:

NM_001099404.2:c.703+206C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001099405.2:c.703+206C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001160160.2:c.703+206C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001160161.2:c.703+206C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354701.2:c.703+206C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000335.5:c.677C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.677C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001494596	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 24, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22028457, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001494596

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 24, 2020)

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

Electrocardiographic characteristics and SCN5A mutations in idiopathic ventricular fibrillation associated with early repolarization.

Watanabe H, Nogami A, Ohkubo K, Kawata H, Hayashi Y, Ishikawa T, Makiyama T, Nagao S, Yagihara N, Takehara N, Kawamura Y, Sato A, Okamura K, Hosaka Y, Sato M, Fukae S, Chinushi M, Oda H, Okabe M, Kimura A, Maemura K, Watanabe I, et al.

Circ Arrhythm Electrophysiol. 2011 Dec;4(6):874-81. doi: 10.1161/CIRCEP.111.963983. Epub 2011 Oct 25.

PubMed [citation]

PMID:: 22028457

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 Invitae, SCV001494596.3

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

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. This variant has been reported to affect SCN5A protein function (PMID: 22028457). This variant has been observed in individual(s) with idiopathic ventricular fibrillation (PMID: 22028457). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with aspartic acid at codon 226 of the SCN5A protein (p.Ala226Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid.

#	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: Jul 29, 2024

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