NM_000335.5(SCN5A):c.569G>C (p.Arg190Pro) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 30, 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:: RCV003770989.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.569G>C (p.Arg190Pro)]

NM_000335.5(SCN5A):c.569G>C (p.Arg190Pro)

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.569G>C (p.Arg190Pro)

HGVS:

NC_000003.12:g.38620885C>G
NG_008934.1:g.33788G>C
NM_000335.5:c.569G>CMANE SELECT
NM_001099404.2:c.569G>C
NM_001099405.2:c.569G>C
NM_001160160.2:c.569G>C
NM_001160161.2:c.569G>C
NM_001354701.2:c.569G>C
NM_198056.3:c.569G>C
NP_000326.2:p.Arg190Pro
NP_001092874.1:p.Arg190Pro
NP_001092875.1:p.Arg190Pro
NP_001153632.1:p.Arg190Pro
NP_001153633.1:p.Arg190Pro
NP_001341630.1:p.Arg190Pro
NP_932173.1:p.Arg190Pro
LRG_289:g.33788G>C
NC_000003.11:g.38662376C>G

Protein change:

R190P

Links:

dbSNP: rs199473069

NCBI 1000 Genomes Browser:

rs199473069

Molecular consequence:

NM_000335.5:c.569G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.569G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.569G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.569G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.569G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.569G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.569G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001542533	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 30, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21908450, 17905336, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001542533

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 30, 2020)

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

Recurrent torsades de pointes after catheter ablation of incessant ventricular bigeminy in combination with QT prolongation.

Reithmann C, Fiek M, Beckmann BM, Kääb S.

Europace. 2012 Feb;14(2):299-300. doi: 10.1093/europace/eur278. Epub 2011 Sep 8.

PubMed [citation]

PMID:: 21908450

Long QT and Brugada syndrome gene mutations in New Zealand.

Chung SK, MacCormick JM, McCulley CH, Crawford J, Eddy CA, Mitchell EA, Shelling AN, French JK, Skinner JR, Rees MI.

Heart Rhythm. 2007 Oct;4(10):1306-14. Epub 2007 Jul 14.

PubMed [citation]

PMID:: 17905336

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001542533.3

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

Description

This sequence change replaces arginine with proline at codon 190 of the SCN5A protein (p.Arg190Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Brugada syndrome (Invitae). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg190 amino acid residue in SCN5A. Other variant(s) that disrupt this residue have been observed in individuals with SCN5A-related conditions (PMID: 21908450, 17905336), which suggests that this may be a clinically significant amino acid residue. 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: Oct 26, 2024

ClinVar

Relating variation to medicine