NM_002234.4(KCNA5):c.1123G>T (p.Glu375Ter) AND Atrial fibrillation, familial, 7

Clinical significance:Pathogenic (Last evaluated: Jul 15, 2006)

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:
RCV000014411.26

Allele description [Variation Report for NM_002234.4(KCNA5):c.1123G>T (p.Glu375Ter)]

NM_002234.4(KCNA5):c.1123G>T (p.Glu375Ter)

Gene:
KCNA5:potassium voltage-gated channel subfamily A member 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12p13.32
Genomic location:
Preferred name:
NM_002234.4(KCNA5):c.1123G>T (p.Glu375Ter)
HGVS:
  • NC_000012.12:g.5045270G>T
  • NG_012198.1:g.6352G>T
  • NM_002234.4:c.1123G>TMANE SELECT
  • NP_002225.2:p.Glu375Ter
  • NC_000012.11:g.5154436G>T
Protein change:
E375*; GLU375TER
Links:
OMIM: 176267.0001; dbSNP: rs121908590
NCBI 1000 Genomes Browser:
rs121908590
Molecular consequence:
  • NM_002234.4:c.1123G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Atrial fibrillation, familial, 7 (ATFB7)
Identifiers:
MONDO: MONDO:0012828; MedGen: C2677106; OMIM: 612240

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000034660OMIMno assertion criteria providedPathogenic
(Jul 15, 2006)
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

Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation.

Olson TM, Alekseev AE, Liu XK, Park S, Zingman LV, Bienengraeber M, Sattiraju S, Ballew JD, Jahangir A, Terzic A.

Hum Mol Genet. 2006 Jul 15;15(14):2185-91. Epub 2006 Jun 13.

PubMed [citation]
PMID:
16772329

Details of each submission

From OMIM, SCV000034660.2

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

Description

In a proband and 2 sibs with isolated atrial fibrillation (ATFB7; 612240), Olson et al. (2006) identified heterozygosity for a 1123G-T transversion in exon 4 of the KCNA5 gene, resulting in a glu375-to-ter (E375X) substitution. The female proband was ascertained at age 35 years, and her daily paroxysms were refractory to pharmacotherapy and radiofrequency ablation. Seven other family members were apparently affected but not genotyped. The mutation was not found in 540 control samples. The truncation eliminated the S4-S6 voltage sensor, pore region, and C terminus, preserving the N terminus and S1-S3 transmembrane domains that secure tetrameric subunit assembly. The pathogenic link between compromised Kv1.5 function and susceptibility to atrial fibrillation was verified in a murine model. Rescue of the genetic defect was achieved by aminoglycoside-induced translational read-through of the E375X premature stop codon, restoring channel function.

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

Last Updated: Oct 7, 2021

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