Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000187818 | SCV000241416 | uncertain significance | not provided | 2014-12-24 | criteria provided, single submitter | clinical testing | p.Val333Ala (GTT>GCT): c.998 T>C in exon 2 of the KCNJ10 gene (NM_002241.4). A variant of unknown significance has been identified in the KCNJ10 gene. The V333A variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is highly conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the V333A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, missense mutations in nearby residues have been not reported in association with KCNJ10-related disorders. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSYV2-1 panel(s). |
Invitae | RCV000796670 | SCV000936193 | uncertain significance | EAST syndrome | 2022-07-12 | criteria provided, single submitter | clinical testing | 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 205830). This variant has not been reported in the literature in individuals affected with KCNJ10-related conditions. This variant is present in population databases (rs750091894, gnomAD 0.0009%). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 333 of the KCNJ10 protein (p.Val333Ala). |