NM_000335.5(SCN5A):c.5708C>T (p.Ser1903Leu) AND not provided

Germline classification:: Conflicting classifications of pathogenicity (4 submissions)
Last evaluated:: Jan 26, 2026
Review status:: criteria provided, conflicting classifications

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:: RCV000058802.29

Allele description [Variation Report for NM_000335.5(SCN5A):c.5708C>T (p.Ser1903Leu)]

NM_000335.5(SCN5A):c.5708C>T (p.Ser1903Leu)

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.5708C>T (p.Ser1903Leu)

Other names:

p.S1904L:TCG>TTG

HGVS:

NC_000003.12:g.38550661G>A
NG_008934.1:g.104012C>T
NM_000335.5:c.5708C>TMANE SELECT
NM_001099404.2:c.5711C>T
NM_001099405.2:c.5657C>T
NM_001160160.2:c.5612C>T
NM_001160161.2:c.5549C>T
NM_001354701.2:c.5654C>T
NM_198056.3:c.5711C>T
NP_000326.2:p.Ser1903Leu
NP_000326.2:p.Ser1903Leu
NP_001092874.1:p.Ser1904Leu
NP_001092875.1:p.Ser1886Leu
NP_001153632.1:p.Ser1871Leu
NP_001153633.1:p.Ser1850Leu
NP_001341630.1:p.Ser1885Leu
NP_932173.1:p.Ser1904Leu
NP_932173.1:p.Ser1904Leu
LRG_289t1:c.5711C>T
LRG_289t2:c.5708C>T
LRG_289:g.104012C>T
LRG_289p1:p.Ser1904Leu
LRG_289p2:p.Ser1903Leu
NC_000003.11:g.38592152G>A
NM_000335.4:c.5708C>T
NM_198056.2:c.5711C>T
c.5711C>T

Protein change:

S1850L

Links:

dbSNP: rs150264233

Molecular consequence:

NM_000335.5:c.5708C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.5711C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.5657C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.5612C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.5549C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.5654C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.5711C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000090322	Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	no classification provided	not provided	germline	literature only	PubMed (5) [See all records that cite these PMIDs] 18708744, 20129283, 22378279, 22426227, 22581653
SCV000235543	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Oct 13, 2023)	germline	clinical testing	Citation Link,
SCV000637187	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 26, 2026)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001713278	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 23, 2019)	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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing, literature only

Citations

PubMed

A novel LQT-3 mutation disrupts an inactivation gate complex with distinct rate-dependent phenotypic consequences.

Bankston JR, Sampson KJ, Kateriya S, Glaaser IW, Malito DL, Chung WK, Kass RS.

Channels (Austin). 2007 Jul-Aug;1(4):273-80. Epub 2007 Aug 31.

PubMed [citation]

PMID:: 18708744

An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.

Kapplinger JD, Tester DJ, Alders M, Benito B, Berthet M, Brugada J, Brugada P, Fressart V, Guerchicoff A, Harris-Kerr C, Kamakura S, Kyndt F, Koopmann TT, Miyamoto Y, Pfeiffer R, Pollevick GD, Probst V, Zumhagen S, Vatta M, Towbin JA, Shimizu W, Schulze-Bahr E, et al.

Heart Rhythm. 2010 Jan;7(1):33-46. doi: 10.1016/j.hrthm.2009.09.069. Epub 2009 Oct 8.

PubMed [citation]

PMID:: 20129283
PMCID:: PMC2822446

See all PubMed Citations (7)

Details of each submission

From Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust, SCV000090322.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (5)

Description

This variant has been reported in the following publications (PMID:18708744;PMID:20129283;PMID:22378279;PMID:22426227).

#	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

From GeneDx, SCV000235543.18

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

Description

LQTS is caused by gain of function variants in the SCN5A channel (NaV1.5), while Brugada syndrome is caused by loss of function variants; as this variant has been identified in individuals with diseases that have different mechanisms of pathogenicity, its clinical significance is uncertain; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22378279, 20129283, 25904541, 28988457, 30847666, 25637381, 22426227, 26159999, 26332594, 24892747, 27435932, 29728395, 26746457, 34021086, 30153324, 21167176, 18708744, 30203441, Tomaselli2023[Functional], 35662881, 24055113)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000637187.10

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

#	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

From Mayo Clinic Laboratories, Mayo Clinic, SCV001713278.1

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

#	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		1	not provided	not provided	not provided

Last Updated: Apr 12, 2026

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