Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000475305 | SCV000552194 | uncertain significance | EAST syndrome | 2022-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 375 of the KCNJ10 protein (p.Arg375His). This variant is present in population databases (rs189596680, gnomAD 0.02%). 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: 411157). 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. |
| Ambry Genetics | RCV002313178 | SCV000847418 | uncertain significance | Inborn genetic diseases | 2019-07-05 | criteria provided, single submitter | clinical testing | The p.R375H variant (also known as c.1124G>A), located in coding exon 1 of the KCNJ10 gene, results from a G to A substitution at nucleotide position 1124. The arginine at codon 375 is replaced by histidine, an amino acid with highly similar properties. 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. |