Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gharavi Laboratory, |
RCV000681895 | SCV000809374 | likely pathogenic | not provided | 2018-09-16 | criteria provided, single submitter | research | |
Molecular Diagnostics Laboratory, |
RCV000021509 | SCV000889954 | pathogenic | X-linked Alport syndrome | 2017-02-23 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000681895 | SCV001222920 | pathogenic | not provided | 2023-01-26 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 24630). For these reasons, this variant has been classified as Pathogenic. 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). 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 missense change has been observed in individual(s) with X-linked dominant Alport syndrome (PMID: 7969679). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1143 of the COL4A5 protein (p.Gly1143Ser). |
Institute of Human Genetics, |
RCV000021509 | SCV001429110 | likely pathogenic | X-linked Alport syndrome | 2017-12-12 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000681895 | SCV001982247 | pathogenic | not provided | 2021-09-28 | criteria provided, single submitter | clinical testing | Reported in multiple individuals with Alport syndrome belonging to a single family in published literature (Renieri et al., 1994; Renieri et al., 1996); however, data is limited; Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL4A5 gene, where the majority of pathogenic missense variants occur, and is predicted to disrupt normal protein folding and function (Stenson et al., 2014; Jais et al., 2000); Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25525159, 8651296, 24077912, 7969679) |
Ce |
RCV000681895 | SCV002564125 | pathogenic | not provided | 2020-09-01 | criteria provided, single submitter | clinical testing | |
Institute Of Human Genetics Munich, |
RCV000021509 | SCV002764652 | pathogenic | X-linked Alport syndrome | 2022-03-08 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000021509 | SCV002778689 | pathogenic | X-linked Alport syndrome | 2022-05-25 | criteria provided, single submitter | clinical testing |