NM_000335.5(SCN5A):c.3282G>T (p.Trp1094Cys) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 11, 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:: RCV002446970.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.3282G>T (p.Trp1094Cys)]

NM_000335.5(SCN5A):c.3282G>T (p.Trp1094Cys)

Genes:

LOC110121269:VISTA enhancer hs2177 [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.3282G>T (p.Trp1094Cys)

HGVS:

NC_000003.12:g.38579439C>A
NG_008934.1:g.75234G>T
NG_053884.1:g.1178C>A
NM_000335.5:c.3282G>TMANE SELECT
NM_001099404.2:c.3285G>T
NM_001099405.2:c.3285G>T
NM_001160160.2:c.3282G>T
NM_001160161.2:c.3228+1492G>T
NM_001354701.2:c.3282G>T
NM_198056.3:c.3285G>T
NP_000326.2:p.Trp1094Cys
NP_001092874.1:p.Trp1095Cys
NP_001092875.1:p.Trp1095Cys
NP_001153632.1:p.Trp1094Cys
NP_001341630.1:p.Trp1094Cys
NP_932173.1:p.Trp1095Cys
NP_932173.1:p.Trp1095Cys
LRG_289t1:c.3285G>T
LRG_289:g.75234G>T
LRG_289p1:p.Trp1095Cys
NC_000003.11:g.38620930C>A
NM_198056.2:c.3285G>T

Protein change:

W1094C

Links:

dbSNP: rs759924541

NCBI 1000 Genomes Browser:

rs759924541

Molecular consequence:

NM_001160161.2:c.3228+1492G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000335.5:c.3282G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.3285G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.3285G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.3282G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.3282G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.3285G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002611512	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 11, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26669661, 29574140 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002611512

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 11, 2020)

germline

clinical testing

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

Citation Link

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

Asymmetry of parental origin in long QT syndrome: preferential maternal transmission of KCNQ1 variants linked to channel dysfunction.

Itoh H, Berthet M, Fressart V, Denjoy I, Maugenre S, Klug D, Mizusawa Y, Makiyama T, Hofman N, Stallmeyer B, Zumhagen S, Shimizu W, Wilde AA, Schulze-Bahr E, Horie M, Tezenas du Montcel S, Guicheney P.

Eur J Hum Genet. 2016 Aug;24(8):1160-6. doi: 10.1038/ejhg.2015.257. Epub 2015 Dec 16.

PubMed [citation]

PMID:: 26669661
PMCID:: PMC4970673

Copy number variations of SCN5A in Brugada syndrome.

Sonoda K, Ohno S, Ozawa J, Hayano M, Hattori T, Kobori A, Yahata M, Aburadani I, Watanabe S, Matsumoto Y, Makiyama T, Horie M.

Heart Rhythm. 2018 Aug;15(8):1179-1188. doi: 10.1016/j.hrthm.2018.03.033. Epub 2018 Mar 21.

PubMed [citation]

PMID:: 29574140

Details of each submission

From Ambry Genetics, SCV002611512.2

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

Description

The p.W1095C variant (also known as c.3285G>T), located in coding exon 17 of the SCN5A gene, results from a G to T substitution at nucleotide position 3285. The tryptophan at codon 1095 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration was detected in two individuals from one family with long QT syndrome (LQTS) family; however, specific phenotypic information was not provided (Itoh H et al. Eur. J. Hum. Genet., 2016 08;24:1160-6). In addition, this alteration was detected once in a cohort of individuals with brugada syndrome who were symptomatic or had a family history of brugada syndrome, sudden death, syncope, or arrhythmic diseases (Sonoda K et al. Heart Rhythm, 2018 08;15:1179-1188). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Jun 9, 2024

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