Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000218716 | SCV000271397 | pathogenic | Rare genetic deafness | 2016-01-12 | criteria provided, single submitter | clinical testing | The p.Arg371X variant in MITF has been identified by our laboratory in one indiv idual with hearing loss, which is assumed to have occurred de novo. It has not been reported in large population studies. This nonsense variant leads to a pr emature termination codon at position 371 and is located 51 nucleotides from the end of the penultimate (second to last) exon. Therefore, this variant is expect ed to undergo nonsense mediated mRNA decay (NMD) (Holbrook 2004) resulting in a n absent protein. However, due to its close location to the penultimate intron it could escape NMD and leading to a truncated protein. Heterozygous loss of fu nction variants in the MITF gene are well described in individuals with Waardenb urg syndrome. In summary, the p.Arg371X variant meets the criteria to be classi fied as pathogenic for hearing loss in an autosomal dominant manner. |
| Genetic Testing Center for Deafness, |
RCV001290157 | SCV001478214 | pathogenic | Waardenburg syndrome type 2A | 2019-01-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004719764 | SCV005325770 | likely pathogenic | not provided | 2023-10-31 | criteria provided, single submitter | clinical testing | Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 150 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34142234, 27759048) |