Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000054388 | SCV001514397 | likely pathogenic | Pulmonary hypertension, primary, 4 | 2024-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 182 of the KCNK3 protein (p.Glu182Lys). This variant is present in population databases (rs398123042, gnomAD 0.007%). This missense change has been observed in individuals with pulmonary arterial hypertension (PMID: 23883380, 29743074; internal data). ClinVar contains an entry for this variant (Variation ID: 60482). 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 expected to disrupt KCNK3 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects KCNK3 function (PMID: 23883380, 28889099). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
OMIM | RCV000054388 | SCV000082865 | pathogenic | Pulmonary hypertension, primary, 4 | 2013-07-25 | no assertion criteria provided | literature only |