U.S. flag

An official website of the United States government

NM_000335.5(SCN5A):c.4421A>T (p.Gln1474Leu) AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 24, 2014
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:
RCV000183076.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.4421A>T (p.Gln1474Leu)]

NM_000335.5(SCN5A):c.4421A>T (p.Gln1474Leu)

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.4421A>T (p.Gln1474Leu)
Other names:
p.Q1475L:CAA>CTA
HGVS:
  • NC_000003.12:g.38556454T>A
  • NG_008934.1:g.98219A>T
  • NM_000335.5:c.4421A>TMANE SELECT
  • NM_001099404.2:c.4424A>T
  • NM_001099405.2:c.4370A>T
  • NM_001160160.2:c.4421A>T
  • NM_001160161.2:c.4262A>T
  • NM_001354701.2:c.4367A>T
  • NM_198056.3:c.4424A>T
  • NP_000326.2:p.Gln1474Leu
  • NP_001092874.1:p.Gln1475Leu
  • NP_001092875.1:p.Gln1457Leu
  • NP_001153632.1:p.Gln1474Leu
  • NP_001153633.1:p.Gln1421Leu
  • NP_001341630.1:p.Gln1456Leu
  • NP_932173.1:p.Gln1475Leu
  • NP_932173.1:p.Gln1475Leu
  • LRG_289t1:c.4424A>T
  • LRG_289:g.98219A>T
  • LRG_289p1:p.Gln1475Leu
  • NC_000003.11:g.38597945T>A
  • NM_198056.2:c.4424A>T
Protein change:
Q1421L
Links:
dbSNP: rs794728885
NCBI 1000 Genomes Browser:
rs794728885
Molecular consequence:
  • NM_000335.5:c.4421A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.4424A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.4370A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.4421A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.4262A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.4367A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.4424A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: CN517202

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000235485GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Likely pathogenic
(Apr 24, 2014) 		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, SCV000235485.10

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

Description

A Q1475L variant that is likely pathogenic was identified in the SCN5A gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The Q1475L variant was not observed in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q1475L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and is reported to be an important region of the sodium channel known as the inactivation gate (Moreau et al., 2013). In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (F1473C, F1473S, Q1476R) have been reported in association with LQTS, supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded.The variant is found in LQT panel(s).

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

Last Updated: Nov 5, 2022