Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000007894 | SCV003523914 | likely pathogenic | EAST syndrome | 2022-07-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 77 of the KCNJ10 protein (p.Gly77Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of SeSAME syndrome (PMID: 19420365). ClinVar contains an entry for this variant (Variation ID: 7468). 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"). Experimental studies have shown that this missense change affects KCNJ10 function (PMID: 19420365, 20807765, 21088294). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| OMIM | RCV000007894 | SCV000028099 | pathogenic | EAST syndrome | 2010-11-12 | no assertion criteria provided | literature only |