NM_000335.5(SCN5A):c.3723C>G (p.Ala1241=) AND not specified

Germline classification:: Likely benign (1 submission)
Last evaluated:: May 16, 2023
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:: RCV003236353.1

Allele description [Variation Report for NM_000335.5(SCN5A):c.3723C>G (p.Ala1241=)]

NM_000335.5(SCN5A):c.3723C>G (p.Ala1241=)

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.3723C>G (p.Ala1241=)

HGVS:

NC_000003.12:g.38566523G>C
NG_008934.1:g.88150C>G
NM_000335.5:c.3723C>GMANE SELECT
NM_001099404.2:c.3726C>G
NM_001099405.2:c.3726C>G
NM_001160160.2:c.3723C>G
NM_001160161.2:c.3564C>G
NM_001354701.2:c.3723C>G
NM_198056.3:c.3726C>G
NP_000326.2:p.Ala1241=
NP_000326.2:p.Ala1241=
NP_001092874.1:p.Ala1242=
NP_001092874.1:p.Ala1242=
NP_001092875.1:p.Ala1242=
NP_001153632.1:p.Ala1241=
NP_001153633.1:p.Ala1188=
NP_001341630.1:p.Ala1241=
NP_932173.1:p.Ala1242=
NP_932173.1:p.Ala1242=
LRG_289t1:c.3726C>G
LRG_289t2:c.3723C>G
LRG_289t3:c.3726C>G
LRG_289:g.88150C>G
LRG_289p1:p.Ala1242=
LRG_289p2:p.Ala1241=
LRG_289p3:p.Ala1242=
NC_000003.11:g.38608014G>C
NM_000335.4:c.3723C>G
NM_001099404.1:c.3726C>G
NM_198056.2:c.3726C>G
NR_176299.1:n.4472C>G

Molecular consequence:

NR_176299.1:n.4472C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000335.5:c.3723C>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001099404.2:c.3726C>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001099405.2:c.3726C>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001160160.2:c.3723C>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001160161.2:c.3564C>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001354701.2:c.3723C>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_198056.3:c.3726C>G - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV003934253	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (May 16, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003934253

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely benign
(May 16, 2023)

germline

clinical testing

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

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

Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval.

Ghouse J, Have CT, Weeke P, Bille Nielsen J, Ahlberg G, Balslev-Harder M, Appel EV, Skaaby T, Olesen SP, Grarup N, Linneberg A, Pedersen O, Haunsø S, Hastrup Svendsen J, Hansen T, Kanters JK, Salling Olesen M.

Eur Heart J. 2015 Oct 1;36(37):2523-9. doi: 10.1093/eurheartj/ehv297. Epub 2015 Jul 9.

PubMed [citation]

PMID:: 26159999

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003934253.1

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

Description

Variant summary: SCN5A c.3726C>G alters a conserved nucleotide resulting in a synonymous change. The variant was absent in 251198 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3726C>G has been reported in the literature showing carriers of the variant had normal mean QTc intervals compared with non-carriers on average (Ghouse_2015), suggesting a more benign role of the variant in the context of congenital long QT syndrome. These report(s) 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. The following publication has been ascertained in the context of this evaluation (PMID: 26159999). No clinical diagnostic laboratories have submitted clinical-significance assessments for the c.3726C>G variant to ClinVar after 2014. However, a different nucleotide change resulting in the same p.A1242= variant was scored as benign or likely benign in ClinVar. Based on the evidence outlined above, the variant was classified as likely benign.

#	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: Jun 24, 2023

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