Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000825626 | SCV000966980 | pathogenic | Rare genetic deafness | 2018-05-07 | criteria provided, single submitter | clinical testing | The p.Ser388X variant in PAX3 has not been previously reported in individuals wi th Waardenburg syndrome and was absent from large population studies. This nons ense variant leads to a premature termination codon at position 388, which is pr edicted to lead to a truncated or absent protein. Heterozygous loss of function of the PAX3 gene is an established disease mechanism in Waardenburg syndrome. In summary, this variant meets criteria to be classified as pathogenic for autos omal dominant Waardenburg syndrome based on the predicted impact of the variant, absence from controls, and presence in an individual with clinical features of Waardenburg syndrome. ACMG/AMP Criteria applied: PVS1, PM2, PP4. |