Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001576748 | SCV001803998 | uncertain significance | not provided | 2024-06-11 | criteria provided, single submitter | clinical testing | In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26850479) |
Labcorp Genetics |
RCV002568491 | SCV003518108 | uncertain significance | Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8 | 2024-01-06 | 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 399 of the MITF protein (p.Gly399Arg). This variant is present in population databases (rs531830542, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of MITF-related conditions (PMID: 26850479). ClinVar contains an entry for this variant (Variation ID: 1208422). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MITF 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. |