NM_000335.5(SCN5A):c.4780G>A (p.Asp1594Asn) AND Progressive familial heart block, type 1A

Clinical significance:Pathogenic (Last evaluated: Jan 22, 2002)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000009983.4

Allele description [Variation Report for NM_000335.5(SCN5A):c.4780G>A (p.Asp1594Asn)]

NM_000335.5(SCN5A):c.4780G>A (p.Asp1594Asn)

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.4780G>A (p.Asp1594Asn)
Other names:
p.D1595N:GAC>AAC
HGVS:
  • NC_000003.12:g.38554309C>T
  • NG_008934.1:g.100364G>A
  • NM_000335.5:c.4780G>AMANE SELECT
  • NM_001099404.1:c.4783G>A
  • NM_001099404.2:c.4783G>A
  • NM_001099405.2:c.4729G>A
  • NM_001160160.2:c.4714+66G>A
  • NM_001160161.2:c.4621G>A
  • NM_001354701.2:c.4726G>A
  • NM_198056.2:c.4783G>A
  • NM_198056.3:c.4783G>A
  • NP_000326.2:p.Asp1594Asn
  • NP_001092874.1:p.Asp1595Asn
  • NP_001092874.1:p.Asp1595Asn
  • NP_001092875.1:p.Asp1577Asn
  • NP_001153633.1:p.Asp1541Asn
  • NP_001341630.1:p.Asp1576Asn
  • NP_932173.1:p.Asp1595Asn
  • NP_932173.1:p.Asp1595Asn
  • LRG_289t1:c.4783G>A
  • LRG_289t3:c.4783G>A
  • LRG_289:g.100364G>A
  • LRG_289p1:p.Asp1595Asn
  • LRG_289p3:p.Asp1595Asn
  • NC_000003.11:g.38595800C>T
  • Q14524:p.Asp1595Asn
Protein change:
D1541N; ASP1595ASN
Links:
UniProtKB: Q14524#VAR_017683; OMIM: 600163.0017; dbSNP: rs137854607
NCBI 1000 Genomes Browser:
rs137854607
Molecular consequence:
  • NM_001160160.2:c.4714+66G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000335.5:c.4780G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.1:c.4783G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.4783G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.4729G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.4621G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.4726G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.2:c.4783G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.4783G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Progressive familial heart block, type 1A (PFHB1A)
Synonyms:
HEART BLOCK, PROGRESSIVE FAMILIAL, TYPE I; Heart block progressive familial type 1; Cardiac conduction defect progressive; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007240; MedGen: C1879286; Orphanet: 871; OMIM: 113900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000030204OMIMno assertion criteria providedPathogenic
(Jan 22, 2002)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block.

Wang DW, Viswanathan PC, Balser JR, George AL Jr, Benson DW.

Circulation. 2002 Jan 22;105(3):341-6.

PubMed [citation]
PMID:
11804990

Details of each submission

From OMIM, SCV000030204.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

Wang et al. (2002) reported a family in which the proband had presented with first-degree atrioventricular block at the age of 9, progressing to complete AV block by the age of 20 (PFHB1A; 113900). The proband's sister and father had electrocardiographic evidence of right bundle branch block and left axis deviation with normal PR intervals. The corrected QT interval was normal (less than 420 ms) in all 3 individuals. Sequencing of the coding region of SCN5A revealed a G-to-A mutation at nucleotide position 4783, which replaced an aspartic acid residue at amino acid position 1595 with asparagine (D1595N). The G4783A mutation was engineered into a recombinant human heart sodium channel and transiently coexpressed with human sodium channel beta-1 subunit (600760) in a cultured mammalian cell line (tsA201). Functional characterization using a patch-clamp technique revealed a significant defect in the kinetics of fast-channel inactivation distinct from those of SCN5A mutations reported in LQT3 (603830). The authors considered this a plausible mechanism for the observed conduction system disease in this family.

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

Last Updated: Nov 27, 2021

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