NM_000335.5(SCN5A):c.1218C>A (p.Asn406Lys) AND SCN5A-related disorder

Germline classification:: Pathogenic (1 submission)
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:: RCV004545744.1

Allele description [Variation Report for NM_000335.5(SCN5A):c.1218C>A (p.Asn406Lys)]

NM_000335.5(SCN5A):c.1218C>A (p.Asn406Lys)

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.1218C>A (p.Asn406Lys)

Other names:

p.N406K:AAC>AAA

HGVS:

NC_000003.12:g.38606071G>T
NG_008934.1:g.48602C>A
NM_000335.5:c.1218C>AMANE SELECT
NM_001099404.1:c.1218C>A
NM_001099404.2:c.1218C>A
NM_001099405.2:c.1218C>A
NM_001160160.2:c.1218C>A
NM_001160161.2:c.1218C>A
NM_001354701.2:c.1218C>A
NM_198056.3:c.1218C>A
NP_000326.2:p.Asn406Lys
NP_001092874.1:p.Asn406Lys
NP_001092875.1:p.Asn406Lys
NP_001153632.1:p.Asn406Lys
NP_001153633.1:p.Asn406Lys
NP_001341630.1:p.Asn406Lys
NP_932173.1:p.Asn406Lys
NP_932173.1:p.Asn406Lys
LRG_289t1:c.1218C>A
LRG_289t3:c.1218C>A
LRG_289:g.48602C>A
LRG_289p1:p.Asn406Lys
NC_000003.11:g.38647562G>T
NM_198056.2:c.1218C>A
Q14524:p.Asn406Lys

Protein change:

N406K

Links:

UniProtKB: Q14524#VAR_055170; dbSNP: rs199473108

NCBI 1000 Genomes Browser:

rs199473108

Molecular consequence:

NM_000335.5:c.1218C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.1218C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.1218C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.1218C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.1218C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.1218C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.1218C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: SCN5A-related disorder
Identifiers:

Recent activity

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SRX19513276 (1)
SRA
cytochrome b, partial (mitochondrion) [Opsariichthys acutipinnis]
cytochrome b, partial (mitochondrion) [Opsariichthys acutipinnis]
gi|1586288326|gb|QBK18674.1|

Protein
interphotoreceptor retinoid-binding protein, partial [Zacco platypus]
interphotoreceptor retinoid-binding protein, partial [Zacco platypus]
gi|2726422769|dbj|BFJ90302.1|

Protein
Zosterops poliogaster winifredae isolate ZMUC O5899 cytochrome b gene, partial c...
Zosterops poliogaster winifredae isolate ZMUC O5899 cytochrome b gene, partial cds; mitochondrial
gi|84373859|gb|DQ328336.1|

Nucleotide
GJB6 gap junction protein beta 6 [Pan troglodytes]
GJB6 gap junction protein beta 6 [Pan troglodytes]
Gene ID:750343

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004046370	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	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

SCV004046370

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV004046370.1

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

Description

This variant has been previously reported in individuals with long QT syndrome and cardiac arrhythmias, including several in whom the variant was reported to be de novo (PMID: 15840476, 24112685, 29983085, 25254341, 32161207). Functional studies have demonstrated that the c.1218C>A (p.Asn406Lys) variant alters sodium channel function (PMID: 24112685, 29983085). The c.1218C>A (p.Asn406Lys) variant is absent from the gnomAD population database and thus is presumed to be rare. It affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.1218C>A (p.Asn406Lys) variant is classified as Pathogenic.

#	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 20, 2024

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