Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000825506 | SCV000966813 | likely pathogenic | Rare genetic deafness | 2018-05-22 | criteria provided, single submitter | clinical testing | The p.Gly846Glu variant in COL4A5 has been identified in one individual by our laboratory with clinical features of Alport syndrome (sensorineural hearing loss , proteinuria, hematuria), and segregated with sensorineural hearing loss in a f ull sibling and a maternal half sibling. The siblings had not been assessed for kidney dysfunction at the time of genetic screening by our laboratory. The p.Gly 846Glu variant was absent from large population studies. The COL4A5 protein has alpha chains that contain long collagenous Gly-X-Y repeats, and missense variant s that affect a Gly residue (such as this variant) are predicted to cause altere d folding of the collagen chains (Tryggvason 1993, Naito 1996, Savige 2016). In addition, 33% of variants identified in Alport syndrome patients reported in the literature are Gly substitutions of one of the Gly-X-Y repeats (Savige 2016). C omputational prediction tools and conservation analysis also suggest that the p. Gly846Glu variant may impact the protein. In summary, although additional studie s are required to fully establish its clinical significance, this variant is lik ely pathogenic. ACMG/AMP Criteria applied: PM1; PM2; PP1; PP3; PP4. |
| Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV000735702 | SCV000863850 | likely pathogenic | X-linked Alport syndrome | 2018-04-17 | no assertion criteria provided | clinical testing |