NM_000335.5(SCN5A):c.73G>A (p.Glu25Lys) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 13, 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:: RCV000171704.12

Allele description [Variation Report for NM_000335.5(SCN5A):c.73G>A (p.Glu25Lys)]

NM_000335.5(SCN5A):c.73G>A (p.Glu25Lys)

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.73G>A (p.Glu25Lys)

HGVS:

NC_000003.12:g.38633235C>T
NG_008934.1:g.21438G>A
NM_000335.5:c.73G>AMANE SELECT
NM_001099404.2:c.73G>A
NM_001099405.2:c.73G>A
NM_001160160.2:c.73G>A
NM_001160161.2:c.73G>A
NM_001354701.2:c.73G>A
NM_198056.3:c.73G>A
NP_000326.2:p.Glu25Lys
NP_001092874.1:p.Glu25Lys
NP_001092875.1:p.Glu25Lys
NP_001153632.1:p.Glu25Lys
NP_001153633.1:p.Glu25Lys
NP_001341630.1:p.Glu25Lys
NP_932173.1:p.Glu25Lys
NP_932173.1:p.Glu25Lys
LRG_289t1:c.73G>A
LRG_289:g.21438G>A
LRG_289p1:p.Glu25Lys
NC_000003.11:g.38674726C>T
NM_198056.2:c.73G>A

Protein change:

E25K

Links:

dbSNP: rs747251132

NCBI 1000 Genomes Browser:

rs747251132

Molecular consequence:

NM_000335.5:c.73G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.73G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.73G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.73G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.73G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.73G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.73G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000055212	Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq	criteria provided, single submitter (Ng et al. (Circ Cardiovasc Genet. 2013))	Uncertain significance (Jun 24, 2013)	unknown	research	PubMed (1) [See all records that cite this PMID]
SCV000814975	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28837624, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000055212

Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq

criteria provided, single submitter

(Ng et al. (Circ Cardiovasc Genet. 2013))

Uncertain significance
(Jun 24, 2013)

unknown

research

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

SCV000814975

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2023)

germline

clinical testing

PubMed (2)
[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
not provided	unknown	unknown	1	not provided	not provided	not provided	not provided	research

Citations

PubMed

Interpreting secondary cardiac disease variants in an exome cohort.

Ng D, Johnston JJ, Teer JK, Singh LN, Peller LC, Wynter JS, Lewis KL, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program..

Circ Cardiovasc Genet. 2013 Aug;6(4):337-46. doi: 10.1161/CIRCGENETICS.113.000039. Epub 2013 Jul 16.

PubMed [citation]

PMID:: 23861362
PMCID:: PMC3887521

Rare variants in genes encoding the cardiac sodium channel and associated compounds and their impact on outcome of catheter ablation of atrial fibrillation.

Husser D, Ueberham L, Hindricks G, Büttner P, Ingram C, Weeke P, Shoemaker MB, Adams V, Arya A, Sommer P, Darbar D, Roden DM, Bollmann A.

PLoS One. 2017;12(8):e0183690. doi: 10.1371/journal.pone.0183690.

PubMed [citation]

PMID:: 28837624
PMCID:: PMC5570360

See all PubMed Citations (3)

Details of each submission

From Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq, SCV000055212.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000814975.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 25 of the SCN5A protein (p.Glu25Lys). This variant is present in population databases (rs747251132, gnomAD 0.003%). This missense change has been observed in individual(s) with atrial fibrillation (PMID: 28837624). ClinVar contains an entry for this variant (Variation ID: 191505). 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.

#	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

ClinVar

Relating variation to medicine