NM_000335.5(SCN5A):c.4068G>A (p.Ala1356=) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 3, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002269271.11

Allele description [Variation Report for NM_000335.5(SCN5A):c.4068G>A (p.Ala1356=)]

NM_000335.5(SCN5A):c.4068G>A (p.Ala1356=)

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.4068G>A (p.Ala1356=)

HGVS:

NC_000003.12:g.38560321C>T
NG_008934.1:g.94352G>A
NM_000335.5:c.4068G>AMANE SELECT
NM_001099404.2:c.4071G>A
NM_001099405.2:c.4071G>A
NM_001160160.2:c.4068G>A
NM_001160161.2:c.3909G>A
NM_001354701.2:c.4068G>A
NM_198056.3:c.4071G>A
NP_000326.2:p.Ala1356=
NP_001092874.1:p.Ala1357=
NP_001092875.1:p.Ala1357=
NP_001153632.1:p.Ala1356=
NP_001153633.1:p.Ala1303=
NP_001341630.1:p.Ala1356=
NP_932173.1:p.Ala1357=
NP_932173.1:p.Ala1357=
LRG_289t1:c.4071G>A
LRG_289:g.94352G>A
LRG_289p1:p.Ala1357=
NC_000003.11:g.38601812C>T
NM_000335.5:c.4068G>A
NM_198056.2:c.4071G>A

Links:

dbSNP: rs187370816

NCBI 1000 Genomes Browser:

rs187370816

Molecular consequence:

NM_000335.5:c.4068G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001099404.2:c.4071G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001099405.2:c.4071G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001160160.2:c.4068G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001160161.2:c.3909G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001354701.2:c.4068G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_198056.3:c.4071G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Functional consequence:

functionally_normal [Sequence Ontology: SO:0002219] - Comment(s)

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
SCV000545072	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 3, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002552918	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jan 20, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000545072

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 3, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002552918

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jan 20, 2022)

germline

clinical testing

Citation Link

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	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, SCV000545072.7

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

Description

This variant is present in population databases (rs187370816, gnomAD 0.01%). This sequence change affects codon 1357 of the SCN5A mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SCN5A protein. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 406438). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions.

#	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, SCV002552918.2

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

Description

Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Reported in ClinVar (ClinVar Variant ID# 406438)

#	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

Last Updated: Oct 26, 2024

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