Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Testing Center for Deafness, |
RCV001290151 | SCV001478209 | likely pathogenic | Waardenburg syndrome type 2A | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV005225359 | SCV005861974 | likely pathogenic | Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8 | 2025-01-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 203 of the MITF protein (p.Arg203Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Waardenburg syndrome (PMID: 34142234). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 995918). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MITF protein function with a positive predictive value of 80%. 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. |
Deafness Molecular Diagnostic Center, |
RCV001290151 | SCV001763642 | likely pathogenic | Waardenburg syndrome type 2A | no assertion criteria provided | case-control |