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NM_000335.5(SCN5A):c.1218C>A (p.Asn406Lys) AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 6, 2018
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:
RCV000182963.3

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)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000235360GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Likely pathogenic
(Jun 6, 2018) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000235360.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The N406K likely pathogenic variant in the SCN5A gene has been reported previously in association with LQTS (Tester et al., 2005; Kato et al., 2014). N406K was reported as apparently de novo in a male with a QTc interval of 638 ms at 1 day old and 478 ms at 8 months old (Kato et al., 2014). The N406K variant is not observed in large population cohorts (Lek et al., 2016). The N406K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Furthermore, functional studies in Chinese hamster ovary cells demonstrated N406 alters the function of this sodium channel (Kato et al., 2014). Nevertheless, the N406K variant lacks observation in a significant number of affected individuals and segregation data, which would further clarify its pathogenicity.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 10, 2024