NM_000335.5(SCN5A):c.5578G>A (p.Val1860Ile) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 18, 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:: RCV003556155.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.5578G>A (p.Val1860Ile)]

NM_000335.5(SCN5A):c.5578G>A (p.Val1860Ile)

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.5578G>A (p.Val1860Ile)

HGVS:

NC_000003.12:g.38550791C>T
NG_008934.1:g.103882G>A
NM_000335.5:c.5578G>AMANE SELECT
NM_001099404.2:c.5581G>A
NM_001099405.2:c.5527G>A
NM_001160160.2:c.5482G>A
NM_001160161.2:c.5419G>A
NM_001354701.2:c.5524G>A
NM_198056.3:c.5581G>A
NP_000326.2:p.Val1860Ile
NP_001092874.1:p.Val1861Ile
NP_001092875.1:p.Val1843Ile
NP_001153632.1:p.Val1828Ile
NP_001153633.1:p.Val1807Ile
NP_001341630.1:p.Val1842Ile
NP_932173.1:p.Val1861Ile
NP_932173.1:p.Val1861Ile
LRG_289t1:c.5581G>A
LRG_289:g.103882G>A
LRG_289p1:p.Val1861Ile
NC_000003.11:g.38592282C>T
NM_198056.2:c.5581G>A

Protein change:

V1807I

Links:

dbSNP: rs199473636

NCBI 1000 Genomes Browser:

rs199473636

Molecular consequence:

NM_000335.5:c.5578G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.5581G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.5527G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.5482G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.5419G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.5524G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.5581G>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
SCV004293478	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 18, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20129283, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004293478

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 18, 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

An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.

Kapplinger JD, Tester DJ, Alders M, Benito B, Berthet M, Brugada J, Brugada P, Fressart V, Guerchicoff A, Harris-Kerr C, Kamakura S, Kyndt F, Koopmann TT, Miyamoto Y, Pfeiffer R, Pollevick GD, Probst V, Zumhagen S, Vatta M, Towbin JA, Shimizu W, Schulze-Bahr E, et al.

Heart Rhythm. 2010 Jan;7(1):33-46. doi: 10.1016/j.hrthm.2009.09.069. Epub 2009 Oct 8.

PubMed [citation]

PMID:: 20129283
PMCID:: PMC2822446

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, SCV004293478.1

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

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1861 of the SCN5A protein (p.Val1861Ile). This missense change has been observed in individual(s) with clinical features of Brugada syndrome (PMID: 20129283). ClinVar contains an entry for this variant (Variation ID: 67999). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.

#	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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