NM_000335.5(SCN5A):c.5365G>A (p.Asp1789Asn) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 25, 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:: RCV003768971.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.5365G>A (p.Asp1789Asn)]

NM_000335.5(SCN5A):c.5365G>A (p.Asp1789Asn)

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.5365G>A (p.Asp1789Asn)

HGVS:

NC_000003.12:g.38551004C>T
NG_008934.1:g.103669G>A
NM_000335.5:c.5365G>AMANE SELECT
NM_001099404.2:c.5368G>A
NM_001099405.2:c.5314G>A
NM_001160160.2:c.5269G>A
NM_001160161.2:c.5206G>A
NM_001354701.2:c.5311G>A
NM_198056.3:c.5368G>A
NP_000326.2:p.Asp1789Asn
NP_001092874.1:p.Asp1790Asn
NP_001092875.1:p.Asp1772Asn
NP_001153632.1:p.Asp1757Asn
NP_001153633.1:p.Asp1736Asn
NP_001341630.1:p.Asp1771Asn
NP_932173.1:p.Asp1790Asn
NP_932173.1:p.Asp1790Asn
LRG_289t1:c.5368G>A
LRG_289:g.103669G>A
LRG_289p1:p.Asp1790Asn
NC_000003.11:g.38592495C>T
NM_198056.2:c.5368G>A

Protein change:

D1736N

Links:

dbSNP: rs772508476

NCBI 1000 Genomes Browser:

rs772508476

Molecular consequence:

NM_000335.5:c.5365G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.5368G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.5314G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.5269G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.5206G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.5311G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.5368G>A - 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
SCV001230788	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 25, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 23200271, 30193851, 9686753, 11150514, 20102920, 26304620, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001230788

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 25, 2023)

germline

clinical testing

PubMed (7)
[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

Autosomal recessive paediatric sick sinus syndrome associated with novel compound mutations in SCN5A.

Kodama T, Serio A, Disertori M, Bronzetti G, Diegoli M, Narula N, Grasso M, Mazzola S, Arbustini E.

Int J Cardiol. 2013 Sep 10;167(6):3078-80. doi: 10.1016/j.ijcard.2012.11.062. Epub 2012 Nov 28. No abstract available.

PubMed [citation]

PMID:: 23200271

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 (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001230788.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1790 of the SCN5A protein (p.Asp1790Asn). This variant is present in population databases (rs772508476, gnomAD 0.003%). This missense change has been observed in individuals with clinical features of SCN5A-related conditions (PMID: 23200271, 30193851; Invitae). ClinVar contains an entry for this variant (Variation ID: 859644). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.Asp1790 amino acid residue in SCN5A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9686753, 11150514, 20102920, 26304620). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.

#	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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