ClinVar Miner

Submissions for variant NM_002234.4(KCNA5):c.1327A>G (p.Ile443Val) (rs370591031)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000557048 SCV000646977 uncertain significance Atrial fibrillation, familial, 7 2017-02-23 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 443 of the KCNA5 protein (p.Ile443Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs370591031, ExAC 0.01%) but has not been reported in the literature in individuals with a KCNA5-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001541143 SCV001759101 uncertain significance not provided 2021-03-09 criteria provided, single submitter clinical testing Reported in a patient with idiopathic pulmonary hypertension (Zhu et al., 2019); however, additional clinical information was not provided; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 469583; Landrum et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31727138)

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