Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001304339 | SCV001493615 | uncertain significance | EAST syndrome | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 345 of the KCNJ10 protein (p.Ser345Gly). This variant is present in population databases (rs752571720, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with KCNJ10-related conditions. ClinVar contains an entry for this variant (Variation ID: 1007194). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KCNJ10 protein function. 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. |
Ambry Genetics | RCV002393722 | SCV002702368 | uncertain significance | Inborn genetic diseases | 2018-06-11 | criteria provided, single submitter | clinical testing | The p.S345G variant (also known as c.1033A>G), located in coding exon 1 of the KCNJ10 gene, results from an A to G substitution at nucleotide position 1033. The serine at codon 345 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |