NM_000335.5(SCN5A):c.44G>C (p.Arg15Thr) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 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:: RCV002326869.9

Allele description [Variation Report for NM_000335.5(SCN5A):c.44G>C (p.Arg15Thr)]

NM_000335.5(SCN5A):c.44G>C (p.Arg15Thr)

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.44G>C (p.Arg15Thr)

HGVS:

NC_000003.12:g.38633264C>G
NG_008934.1:g.21409G>C
NM_000335.5:c.44G>CMANE SELECT
NM_001099404.2:c.44G>C
NM_001099405.2:c.44G>C
NM_001160160.2:c.44G>C
NM_001160161.2:c.44G>C
NM_001354701.2:c.44G>C
NM_198056.3:c.44G>C
NP_000326.2:p.Arg15Thr
NP_001092874.1:p.Arg15Thr
NP_001092875.1:p.Arg15Thr
NP_001153632.1:p.Arg15Thr
NP_001153633.1:p.Arg15Thr
NP_001341630.1:p.Arg15Thr
NP_932173.1:p.Arg15Thr
NP_932173.1:p.Arg15Thr
LRG_289t1:c.44G>C
LRG_289:g.21409G>C
LRG_289p1:p.Arg15Thr
NC_000003.11:g.38674755C>G
NM_198056.2:c.44G>C

Protein change:

R15T

Links:

dbSNP: rs373410109

NCBI 1000 Genomes Browser:

rs373410109

Molecular consequence:

NM_000335.5:c.44G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.44G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.44G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.44G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.44G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.44G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.44G>C - 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
SCV002635416	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (May 10, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25904541, 29033053, 31737537 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002635416

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(May 10, 2022)

germline

clinical testing

PubMed (3)
[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

Enhanced Classification of Brugada Syndrome-Associated and Long-QT Syndrome-Associated Genetic Variants in the SCN5A-Encoded Na(v)1.5 Cardiac Sodium Channel.

Kapplinger JD, Giudicessi JR, Ye D, Tester DJ, Callis TE, Valdivia CR, Makielski JC, Wilde AA, Ackerman MJ.

Circ Cardiovasc Genet. 2015 Aug;8(4):582-95. doi: 10.1161/CIRCGENETICS.114.000831. Epub 2015 Apr 22.

PubMed [citation]

PMID:: 25904541
PMCID:: PMC4878676

Identification and characterization of a novel recessive KCNQ1 mutation associated with Romano-Ward Long-QT syndrome in two Iranian families.

Zafari Z, Dalili M, Zeinali S, Saber S, Fazeli Far AF, Akbari MT.

J Electrocardiol. 2017 Nov - Dec;50(6):912-918. doi: 10.1016/j.jelectrocard.2017.07.012. Epub 2017 Jul 12.

PubMed [citation]

PMID:: 29033053

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002635416.2

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

Description

The p.R15T variant (also known as c.44G>C), located in coding exon 1 of the SCN5A gene, results from a G to C substitution at nucleotide position 44. The arginine at codon 15 is replaced by threonine, an amino acid with similar properties. This alteration has been reported in an arrhythmia cohort with limited clinical details, as well as in a control population and in unaffected family members in a family with long QT syndrome and an additional alteration in KCNQ1 identified (Kapplinger JD et al. Circ Cardiovasc Genet, 2015 Aug;8:582-95; Zafari Z et al. J Electrocardiol, 2017 Jul;50:912-918; Marschall C et al. Cardiovasc Diagn Ther, 2019 Oct;9:S292-S298). 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: Oct 26, 2024

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