Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000825582 | SCV000966922 | likely pathogenic | Rare genetic deafness | 2018-11-14 | criteria provided, single submitter | clinical testing | The p.Leu399ProfsX5 variant in EYA1 has not been previously reported in individu als with hearing loss or branchio-oto-renal spectrum disorder and was absent fro m large population studies. This variant is predicted to cause a frameshift, whi ch alters the protein?s amino acid sequence beginning at position 399 and leads to a premature termination codon 5 amino acids downstream. This alteration is th en predicted to lead to a truncated or absent protein. Loss of function of the E YA1 gene is an established disease mechanism in autosomal dominant branchio-oto- renal syndrome. In summary, although additional studies are required to fully es tablish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant branchio-oto-renal syndrome. ACMG/AM P Criteria applied: PVS1, PM2. |