Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001366510 | SCV001562815 | uncertain significance | EAST syndrome | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with leucine at codon 336 of the KCNJ10 protein (p.Val336Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with KCNJ10-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. |
Gene |
RCV001562858 | SCV001785695 | uncertain significance | not provided | 2021-04-14 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV003246952 | SCV003952245 | uncertain significance | Inborn genetic diseases | 2023-04-07 | criteria provided, single submitter | clinical testing | The c.1006G>C (p.V336L) alteration is located in exon 2 (coding exon 1) of the KCNJ10 gene. This alteration results from a G to C substitution at nucleotide position 1006, causing the valine (V) at amino acid position 336 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |