NM_000335.5(SCN5A):c.4027T>C (p.Phe1343Leu) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 17, 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:: RCV003541452.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.4027T>C (p.Phe1343Leu)]

NM_000335.5(SCN5A):c.4027T>C (p.Phe1343Leu)

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.4027T>C (p.Phe1343Leu)

HGVS:

NC_000003.12:g.38560362A>G
NG_008934.1:g.94311T>C
NM_000335.5:c.4027T>CMANE SELECT
NM_001099404.2:c.4030T>C
NM_001099405.2:c.4030T>C
NM_001160160.2:c.4027T>C
NM_001160161.2:c.3868T>C
NM_001354701.2:c.4027T>C
NM_198056.3:c.4030T>C
NP_000326.2:p.Phe1343Leu
NP_001092874.1:p.Phe1344Leu
NP_001092875.1:p.Phe1344Leu
NP_001153632.1:p.Phe1343Leu
NP_001153633.1:p.Phe1290Leu
NP_001341630.1:p.Phe1343Leu
NP_932173.1:p.Phe1344Leu
NP_932173.1:p.Phe1344Leu
LRG_289t1:c.4030T>C
LRG_289:g.94311T>C
LRG_289p1:p.Phe1344Leu
NC_000003.11:g.38601853A>G
NM_198056.2:c.4030T>C

Protein change:

F1290L

Links:

dbSNP: rs199473228

NCBI 1000 Genomes Browser:

rs199473228

Molecular consequence:

NM_000335.5:c.4027T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.4030T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.4030T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.4027T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.3868T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.4027T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.4030T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002153482	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 17, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16616735, 30193851, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002153482

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 17, 2020)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

A novel SCN5A mutation, F1344S, identified in a patient with Brugada syndrome and fever-induced ventricular fibrillation.

Keller DI, Huang H, Zhao J, Frank R, Suarez V, Delacrétaz E, Brink M, Osswald S, Schwick N, Chahine M.

Cardiovasc Res. 2006 Jun 1;70(3):521-9. Epub 2006 Mar 3.

PubMed [citation]

PMID:: 16616735

Clinical presentation and follow-up of women affected by Brugada syndrome.

Berthome P, Tixier R, Briand J, Geoffroy O, Babuty D, Mansourati J, Jesel L, Dupuis JM, Bru P, Kyndt F, Guyomarch B, Thollet A, Behar N, Mabo P, Sacher F, Probst V, Gourraud JB.

Heart Rhythm. 2019 Feb;16(2):260-267. doi: 10.1016/j.hrthm.2018.08.032. Epub 2018 Sep 5.

PubMed [citation]

PMID:: 30193851

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002153482.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Phe1344 amino acid residue in SCN5A. Other variant(s) that disrupt this residue have been observed in individuals with SCN5A-related conditions (PMID: 16616735), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has been observed in individual(s) with Brugada syndrome (PMID: 30193851). ClinVar contains an entry for this variant (Variation ID: 67850). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 1344 of the SCN5A protein (p.Phe1344Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine.

#	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: Sep 29, 2024

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