Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002536887 | SCV003445834 | pathogenic | not provided | 2022-05-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1161 of the COL4A5 protein (p.Gly1161Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Alport syndrome (PMID: 24130771; Invitae). ClinVar contains an entry for this variant (Variation ID: 635536). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL4A5 protein function. This variant disrupts the triple helix domain of COL4A5. Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL4A5, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 23720012, 27627812) compared to the general population (ExAC). For these reasons, this variant has been classified as Pathogenic. |
| Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV000787006 | SCV000925914 | pathogenic | X-linked Alport syndrome | 2018-12-27 | no assertion criteria provided | clinical testing |