Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001045755 | SCV001209626 | uncertain significance | Long QT syndrome | 2021-05-05 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with KCNJ5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant is present in population databases (rs745968243, ExAC 0.04%). This sequence change replaces lysine with arginine at codon 407 of the KCNJ5 protein (p.Lys407Arg). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and arginine. |
| Fulgent Genetics, |
RCV002481920 | SCV002782398 | uncertain significance | Long QT syndrome 13; Familial hyperaldosteronism type III | 2021-09-23 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004629419 | SCV005124731 | benign | Cardiovascular phenotype | 2024-04-26 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |