Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000659866 | SCV000781748 | uncertain significance | Waardenburg syndrome type 2A | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Genomic Research Center, |
RCV000659866 | SCV000845306 | uncertain significance | Waardenburg syndrome type 2A | 2018-08-07 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV001195616 | SCV001366015 | uncertain significance | not specified | 2019-06-07 | criteria provided, single submitter | clinical testing | The p.Val251Met variant in MITF has been previously identified in one individual with hearing loss and heterochromia iridium by our laboratory and was absent from large population studies. This variant has been reported in ClinVar (Variation ID 547535). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Val251Met variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3, PP4. |
Prevention |
RCV003411566 | SCV004111880 | likely pathogenic | MITF-related disorder | 2023-03-27 | criteria provided, single submitter | clinical testing | The MITF c.751G>A variant is predicted to result in the amino acid substitution p.Val251Met. This variant was reported in a patient with Waardenburg syndrome (Minami et al. 2019. PubMed ID: 30978479), and occurred de novo in a patient with bilateral sensorineural hearing loss (PreventionGenetics, internal data). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. We interpret this variant as likely pathogenic. |