Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV001255344 | SCV001431674 | likely pathogenic | Intellectual disability | 2020-08-03 | criteria provided, single submitter | clinical testing | The variant c.629A>G, p.(Asn210Ser) was identified in an individual with neurodevelopmental disorder (NDD) and classified as Likely pathogenic according to ACMG guidelines. Inheritance for this variant was DNV.The variants does not (fully) explain the NDD in this individual |
Institute of Human Genetics, |
RCV001262546 | SCV001440464 | uncertain significance | Waardenburg syndrome type 2A | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002568750 | SCV003215695 | uncertain significance | Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8 | 2022-06-23 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with MITF-related conditions. This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 210 of the MITF protein (p.Asn210Ser). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 977608). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant disrupts the p.Asn210Lys amino acid residue in MITF. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10851256). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |