ClinVar Miner

Submissions for variant NM_002234.4(KCNA5):c.1580C>T (p.Thr527Met)

gnomAD frequency: 0.00005  dbSNP: rs121908591
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000295612 SCV000340743 uncertain significance not provided 2016-04-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000014412 SCV000812911 uncertain significance Atrial fibrillation, familial, 7 2024-11-04 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 527 of the KCNA5 protein (p.Thr527Met). This variant is present in population databases (rs121908591, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with atrial fibrillation (PMID: 19343045, 20646426, 26129877, 34570182). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 13470). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt KCNA5 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects KCNA5 function (PMID: 20646426, 26129877). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV000014412 SCV002815043 uncertain significance Atrial fibrillation, familial, 7 2021-09-21 criteria provided, single submitter clinical testing
OMIM RCV000014412 SCV000034661 pathogenic Atrial fibrillation, familial, 7 2009-05-01 no assertion criteria provided literature only

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