Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001949480 | SCV002238291 | pathogenic | not provided | 2021-09-15 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with autosomal dominant keratitis–ichthyosis–deafness (KID) syndrome (PMID: 20629838). In at least one individual the variant was observed to be de novo. This sequence change replaces alanine with valine at codon 88 of the GJB2 protein (p.Ala88Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). 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 expected to disrupt GJB2 protein function. Experimental studies have shown that this missense change affects GJB2 function (PMID: 23447037). For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV004565138 | SCV005049771 | pathogenic | Autosomal dominant keratitis-ichthyosis-hearing loss syndrome | 2024-01-08 | criteria provided, single submitter | clinical testing |