NM_000335.5(SCN5A):c.2T>C (p.Met1Thr) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 15, 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:: RCV003657619.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.2T>C (p.Met1Thr)]

NM_000335.5(SCN5A):c.2T>C (p.Met1Thr)

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.2T>C (p.Met1Thr)

HGVS:

NC_000003.12:g.38633306A>G
NG_008934.1:g.21367T>C
NM_000335.5:c.2T>CMANE SELECT
NM_001099404.2:c.2T>C
NM_001099405.2:c.2T>C
NM_001160160.2:c.2T>C
NM_001160161.2:c.2T>C
NM_001354701.2:c.2T>C
NM_198056.3:c.2T>C
NP_000326.2:p.Met1Thr
NP_001092874.1:p.Met1Thr
NP_001092875.1:p.Met1Thr
NP_001153632.1:p.Met1Thr
NP_001153633.1:p.Met1Thr
NP_001341630.1:p.Met1Thr
NP_932173.1:p.Met1Thr
LRG_289:g.21367T>C
NC_000003.11:g.38674797A>G

Protein change:

M1T

Links:

dbSNP: rs2125936074

NCBI 1000 Genomes Browser:

rs2125936074

Molecular consequence:

NM_000335.5:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001099404.2:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001099405.2:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001160160.2:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001160161.2:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001354701.2:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_198056.3:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_000335.5:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Gene Links for GEO Profiles (Select 103825707) (1)
Gene
ANKS1B ankyrin repeat and sterile alpha motif domain containing 1B [Homo sapiens...
ANKS1B ankyrin repeat and sterile alpha motif domain containing 1B [Homo sapiens]
Gene ID:56899

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002287705	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 15, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20609320, 30193851, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002287705

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 15, 2021)

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

The spectrum of SCN5A gene mutations in Spanish Brugada syndrome patients.

García-Castro M, García C, Reguero JR, Miar A, Rubín JM, Alvarez V, Morís C, Coto E.

Rev Esp Cardiol. 2010 Jul;63(7):856-9. English, Spanish.

PubMed [citation]

PMID:: 20609320

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, SCV002287705.4

#	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 a region of the SCN5A protein in which other variant(s) (p.Ala2Thr) have been observed in individuals with SCN5A-related conditions (PMID: 20609320). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Disruption of the initiator codon has been observed in individual(s) with Brugada syndrome (PMID: 30193851). This variant is not present in population databases (ExAC no frequency). This sequence change affects the initiator methionine of the SCN5A mRNA. The next in-frame methionine is located at codon 28.

#	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: Nov 3, 2024

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