NM_000335.5(SCN5A):c.589G>T (p.Asp197Tyr) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 10, 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:: RCV003658427.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.589G>T (p.Asp197Tyr)]

NM_000335.5(SCN5A):c.589G>T (p.Asp197Tyr)

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.589G>T (p.Asp197Tyr)

HGVS:

NC_000003.12:g.38620865C>A
NG_008934.1:g.33808G>T
NM_000335.5:c.589G>TMANE SELECT
NM_001099404.2:c.589G>T
NM_001099405.2:c.589G>T
NM_001160160.2:c.589G>T
NM_001160161.2:c.589G>T
NM_001354701.2:c.589G>T
NM_198056.3:c.589G>T
NP_000326.2:p.Asp197Tyr
NP_001092874.1:p.Asp197Tyr
NP_001092875.1:p.Asp197Tyr
NP_001153632.1:p.Asp197Tyr
NP_001153633.1:p.Asp197Tyr
NP_001341630.1:p.Asp197Tyr
NP_932173.1:p.Asp197Tyr
NP_932173.1:p.Asp197Tyr
LRG_289t1:c.589G>T
LRG_289:g.33808G>T
LRG_289p1:p.Asp197Tyr
NC_000003.11:g.38662356C>A
NM_198056.2:c.589G>T

Protein change:

D197Y

Links:

dbSNP: rs1553605667

NCBI 1000 Genomes Browser:

rs1553605667

Molecular consequence:

NM_000335.5:c.589G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.589G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.589G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.589G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.589G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.589G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.589G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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peptidase inhibitor R3HDML precursor [Homo sapiens]
peptidase inhibitor R3HDML precursor [Homo sapiens]
gi|30425410|ref|NP_848586.1|

Protein
Mctp2 multiple C2 and transmembrane domain containing 2 [Rattus norvegicus]
Mctp2 multiple C2 and transmembrane domain containing 2 [Rattus norvegicus]
Gene ID:308742

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003310639	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 10, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31477192, 33221895, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003310639

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 10, 2022)

germline

clinical testing

PubMed (3)
[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

Clinical characterisation of a novel SCN5A variant associated with progressive malignant arrhythmia and dilated cardiomyopathy.

Kean AC, Helm BM, Vatta M, Ayers MD, Parent JJ, Darragh RK.

Cardiol Young. 2019 Oct;29(10):1257-1263. doi: 10.1017/S1047951119001860.

PubMed [citation]

PMID:: 31477192

Brugada syndrome genetics is associated with phenotype severity.

Ciconte G, Monasky MM, Santinelli V, Micaglio E, Vicedomini G, Anastasia L, Negro G, Borrelli V, Giannelli L, Santini F, de Innocentiis C, Rondine R, Locati ET, Bernardini A, Mazza BC, Mecarocci V, Ćalović Ž, Ghiroldi A, D'Imperio S, Benedetti S, Di Resta C, Rivolta I, et al.

Eur Heart J. 2021 Mar 14;42(11):1082-1090. doi: 10.1093/eurheartj/ehaa942.

PubMed [citation]

PMID:: 33221895
PMCID:: PMC7955973

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003310639.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

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 disrupts the p.Asp197 amino acid residue in SCN5A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31477192; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 201435). This missense change has been observed in individual(s) with SCN5A-related conditions (PMID: 33221895). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 197 of the SCN5A protein (p.Asp197Tyr).

#	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: Oct 13, 2024

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