NM_000335.5(SCN5A):c.2948G>A (p.Gly983Asp) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 5, 2022
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:: RCV002436737.9

Allele description [Variation Report for NM_000335.5(SCN5A):c.2948G>A (p.Gly983Asp)]

NM_000335.5(SCN5A):c.2948G>A (p.Gly983Asp)

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.2948G>A (p.Gly983Asp)

HGVS:

NC_000003.12:g.38581211C>T
NG_008934.1:g.73462G>A
NG_053884.1:g.2950C>T
NM_000335.5:c.2948G>AMANE SELECT
NM_001099404.2:c.2948G>A
NM_001099405.2:c.2948G>A
NM_001160160.2:c.2948G>A
NM_001160161.2:c.2948G>A
NM_001354701.2:c.2948G>A
NM_198056.3:c.2948G>A
NP_000326.2:p.Gly983Asp
NP_001092874.1:p.Gly983Asp
NP_001092875.1:p.Gly983Asp
NP_001153632.1:p.Gly983Asp
NP_001153633.1:p.Gly983Asp
NP_001341630.1:p.Gly983Asp
NP_932173.1:p.Gly983Asp
LRG_289t1:c.2948G>A
LRG_289:g.73462G>A
NC_000003.11:g.38622702C>T
NC_000003.11:g.38622702C>T
NM_198056.2:c.2948G>A

Protein change:

G983D

Links:

dbSNP: rs766096031

NCBI 1000 Genomes Browser:

rs766096031

Molecular consequence:

NM_000335.5:c.2948G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.2948G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.2948G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.2948G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.2948G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.2948G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.2948G>A - 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
SCV002749999	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jul 5, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002749999

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jul 5, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Electrophysiological characterization of a large set of novel variants in the SCN5A-gene: identification of novel LQTS3 and BrS mutations.

Ortiz-Bonnin B, Rinné S, Moss R, Streit AK, Scharf M, Richter K, Stöber A, Pfeufer A, Seemann G, Kääb S, Beckmann BM, Decher N.

Pflugers Arch. 2016 Aug;468(8):1375-87. doi: 10.1007/s00424-016-1844-3. Epub 2016 Jun 11.

PubMed [citation]

PMID:: 27287068

Details of each submission

From Ambry Genetics, SCV002749999.2

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

Description

The p.G983D variant (also known as c.2948G>A), located in coding exon 16 of the SCN5A gene, results from a G to A substitution at nucleotide position 2948. The glycine at codon 983 is replaced by aspartic acid, an amino acid with similar properties. This alteration was reported in a subject with abnormal T waves who was noted to have a normal QTc interval. and functional studies by this group suggested gain of function (Ortiz-Bonnin B et al. Pflugers Arch, 2016 08;468:1375-87). This amino acid position is not well 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 2, 2024

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