NM_000335.5(SCN5A):c.3944G>C (p.Arg1315Pro) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 3, 2021
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:: RCV001420834.1

Allele description [Variation Report for NM_000335.5(SCN5A):c.3944G>C (p.Arg1315Pro)]

NM_000335.5(SCN5A):c.3944G>C (p.Arg1315Pro)

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.3944G>C (p.Arg1315Pro)

HGVS:

NC_000003.12:g.38562431C>G
NG_008934.1:g.92242G>C
NM_000335.5:c.3944G>CMANE SELECT
NM_001099404.2:c.3947G>C
NM_001099405.2:c.3947G>C
NM_001160160.2:c.3944G>C
NM_001160161.2:c.3785G>C
NM_001354701.2:c.3944G>C
NM_198056.3:c.3947G>C
NP_000326.2:p.Arg1315Pro
NP_001092874.1:p.Arg1316Pro
NP_001092875.1:p.Arg1316Pro
NP_001153632.1:p.Arg1315Pro
NP_001153633.1:p.Arg1262Pro
NP_001341630.1:p.Arg1315Pro
NP_932173.1:p.Arg1316Pro
LRG_289t1:c.3947G>C
LRG_289:g.92242G>C
NC_000003.11:g.38603922C>G
NM_198056.2:c.3947G>C

Protein change:

R1262P

Links:

dbSNP: rs765907469

NCBI 1000 Genomes Browser:

rs765907469

Molecular consequence:

NM_000335.5:c.3944G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.3947G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.3947G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.3944G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.3785G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.3944G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.3947G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001623226	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (May 3, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24631775, 29247119 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001623226

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(May 3, 2021)

germline

clinical testing

PubMed (2)
[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

Cardiac channelopathy testing in 274 ethnically diverse sudden unexplained deaths.

Wang D, Shah KR, Um SY, Eng LS, Zhou B, Lin Y, Mitchell AA, Nicaj L, Prinz M, McDonald TV, Sampson BA, Tang Y.

Forensic Sci Int. 2014 Apr;237:90-9. doi: 10.1016/j.forsciint.2014.01.014. Epub 2014 Feb 15.

PubMed [citation]

PMID:: 24631775

Applying High-Resolution Variant Classification to Cardiac Arrhythmogenic Gene Testing in a Demographically Diverse Cohort of Sudden Unexplained Deaths.

Lin Y, Williams N, Wang D, Coetzee W, Zhou B, Eng LS, Um SY, Bao R, Devinsky O, McDonald TV, Sampson BA, Tang Y.

Circ Cardiovasc Genet. 2017 Dec;10(6). doi:pii: e001839. 10.1161/CIRCGENETICS.117.001839.

PubMed [citation]

PMID:: 29247119

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001623226.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: SCN5A c.3947G>C (p.Arg1316Pro) results in a non-conservative amino acid change located in the Ion transport domain (IPR005821) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 241678 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3947G>C has been reported in the literature in at least an individual affected with sudden unexplained death (Lin_2017, Wang_2014). These reports however, do not provide unequivocal conclusions about association of the variant with Arrhythmia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as 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: Dec 24, 2023

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