NM_000335.5(SCN5A):c.3704A>G (p.Lys1235Arg) AND Cardiac arrhythmia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 28, 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:: RCV001842344.10

Allele description [Variation Report for NM_000335.5(SCN5A):c.3704A>G (p.Lys1235Arg)]

NM_000335.5(SCN5A):c.3704A>G (p.Lys1235Arg)

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.3704A>G (p.Lys1235Arg)

HGVS:

NC_000003.12:g.38566542T>C
NG_008934.1:g.88131A>G
NM_000335.4:c.3704A>G
NM_000335.5:c.3704A>GMANE SELECT
NM_001099404.2:c.3707A>G
NM_001099405.2:c.3707A>G
NM_001160160.2:c.3704A>G
NM_001160161.2:c.3545A>G
NM_001354701.2:c.3704A>G
NM_198056.3:c.3707A>G
NP_000326.2:p.Lys1235Arg
NP_001092874.1:p.Lys1236Arg
NP_001092875.1:p.Lys1236Arg
NP_001153632.1:p.Lys1235Arg
NP_001153633.1:p.Lys1182Arg
NP_001341630.1:p.Lys1235Arg
NP_932173.1:p.Lys1236Arg
NP_932173.1:p.Lys1236Arg
LRG_289t1:c.3707A>G
LRG_289t2:c.3704A>G
LRG_289:g.88131A>G
LRG_289p1:p.Lys1236Arg
NC_000003.11:g.38608033T>C
NM_198056.2:c.3707A>G

Protein change:

K1182R

Links:

dbSNP: rs199473209

NCBI 1000 Genomes Browser:

rs199473209

Molecular consequence:

NM_000335.5:c.3704A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.3707A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.3707A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.3704A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.3545A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.3704A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.3707A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiac arrhythmia
Synonyms:: Cardiac rhythm disease
Identifiers:: EFO: EFO_0004269; MONDO: MONDO:0007263; MedGen: C0003811; Human Phenotype Ontology: HP:0011675

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001736301	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 28, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001736301

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 28, 2020)

germline

clinical testing

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

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001736301.1

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

Description

This missense variant replaces lysine with arginine at codon 1236 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a study population with families affected with Brugada syndrome (PMID: 21126620). This variant has been identified in 1/250732 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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: Nov 10, 2024

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