• delete

NM_198056.2(SCN5A):c.3392C>T (p.Thr1131Ile) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Jun 24, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000183033.2

Allele description

NM_198056.2(SCN5A):c.3392C>T (p.Thr1131Ile)

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_198056.2(SCN5A):c.3392C>T (p.Thr1131Ile)
Other names:
p.T1131I:ACC>ATC
HGVS:
  • NC_000003.12:g.38576780G>A
  • NG_008934.1:g.77893C>T
  • NM_000335.4:c.3389C>T
  • NM_001099404.1:c.3392C>T
  • NM_001099405.1:c.3392C>T
  • NM_001160160.2:c.3389C>T
  • NM_001160161.1:c.3230C>T
  • NM_001354701.2:c.3389C>T
  • NM_198056.2:c.3392C>T
  • NP_000326.2:p.Thr1130Ile
  • NP_001092874.1:p.Thr1131Ile
  • NP_001092875.1:p.Thr1131Ile
  • NP_001153632.1:p.Thr1130Ile
  • NP_001153633.1:p.Thr1077Ile
  • NP_001341630.1:p.Thr1130Ile
  • NP_932173.1:p.Thr1131Ile
  • LRG_289t1:c.3392C>T
  • LRG_289t2:c.3389C>T
  • LRG_289t3:c.3392C>T
  • LRG_289:g.77893C>T
  • LRG_289p1:p.Thr1131Ile
  • LRG_289p2:p.Thr1130Ile
  • LRG_289p3:p.Thr1131Ile
  • NC_000003.11:g.38618271G>A
  • Q14524:p.Thr1131Ile
Protein change:
T1077I
Links:
UniProtKB: Q14524#VAR_055186; dbSNP: rs199473197
NCBI 1000 Genomes Browser:
rs199473197
Molecular consequence:
  • NM_000335.4:c.3389C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.1:c.3392C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.1:c.3392C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.3389C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.1:c.3230C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.3389C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.2:c.3392C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000235441GeneDxcriteria provided, single submitter
Uncertain significance
(Jun 24, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000235441.10

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

Description

The T1131I variant of uncertain significance in the SCN5A gene was originally reported in an African Americanindividual who was diagnosed with atrial fibrillation in conjunction with underlying structural heart disease at age 42(Darbar et al., 2008). In a subsequent analysis of 274 sudden unexplained death cases with negative autopsy findings,T1131I was reported in one African American infant who died at two weeks of age while co-sleeping (Wang et al.,2014). The T1131I variant has also been identified independently and/or in conjunction with additional cardiogeneticvariants in individuals referred for cardiomyopathy/arrhythmia genetic testing at GeneDx; however, segregation data islimited or absent for these individuals due to the lack of clinical information provided and/or insufficient participationby informative family members. The T1131I variant was absent in 720 published control alleles of matched ethnicbackgrounds (Darbar et al., 2008), and was not observed with any significant frequency in approximately 6,400individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The T1131I variantis a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residuesdiffer in polarity, charge, size and/or other properties. Nevertheless, this substitution occurs at a position that is notconserved. Consequently, in silico analysis predicts this variant likely does not alter the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.

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

Last Updated: Jun 14, 2021

Support Center