NM_000335.5(SCN5A):c.4694_4695delinsAA (p.Leu1565Gln) AND Brugada syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 15, 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:: RCV001309526.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.4694_4695delinsAA (p.Leu1565Gln)]

NM_000335.5(SCN5A):c.4694_4695delinsAA (p.Leu1565Gln)

Gene:

SCN5A:sodium voltage-gated channel alpha subunit 5 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000335.5(SCN5A):c.4694_4695delinsAA (p.Leu1565Gln)

HGVS:

NC_000003.12:g.38554394_38554395delinsTT
NG_008934.1:g.100278_100279delinsAA
NM_000335.5:c.4694_4695delinsAAMANE SELECT
NM_001099404.2:c.4697_4698delinsAA
NM_001099405.2:c.4643_4644delinsAA
NM_001160160.2:c.4694_4695delinsAA
NM_001160161.2:c.4535_4536delinsAA
NM_001354701.2:c.4640_4641delinsAA
NM_198056.3:c.4697_4698delinsAA
NP_000326.2:p.Leu1565Gln
NP_001092874.1:p.Leu1566Gln
NP_001092875.1:p.Leu1548Gln
NP_001153632.1:p.Leu1565Gln
NP_001153633.1:p.Leu1512Gln
NP_001341630.1:p.Leu1547Gln
NP_932173.1:p.Leu1566Gln
LRG_289:g.100278_100279delinsAA
NC_000003.11:g.38595885_38595886delinsTT

Protein change:

L1512Q

Links:

dbSNP: rs2061096389

NCBI 1000 Genomes Browser:

rs2061096389

Molecular consequence:

NM_000335.5:c.4694_4695delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.4697_4698delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.4643_4644delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.4694_4695delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.4535_4536delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.4640_4641delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.4697_4698delinsAA - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Brugada syndrome
Synonyms:: Sudden unexpected nocturnal death syndrome; Sudden unexplained nocturnal death syndrome; Sudden Unexplained Death Syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015263; MedGen: C1142166; OMIM: PS601144

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001499027	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 15, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001499027

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 15, 2020)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001499027.1

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

Description

This sequence change replaces leucine with glutamine at codon 1566 of the SCN5A protein (p.Leu1566Gln). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN5A-related conditions. 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: Not Available; PolyPhen-2: Probably Damaging; Align-GVGD: Not Available). 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.

#	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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