Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Human Genetics Munich, |
RCV000995728 | SCV001150053 | pathogenic | Autosomal recessive Alport syndrome | 2018-11-16 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001858820 | SCV002260519 | uncertain significance | not provided | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 611 of the COL4A3 protein (p.Gly611Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with COL4A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 807567). 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 COL4A3 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Gene |
RCV001858820 | SCV004034889 | pathogenic | not provided | 2023-10-30 | criteria provided, single submitter | clinical testing | Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL4A3 gene, where the majority of pathogenic missense variants occur, and is predicted to disrupt normal protein folding and function (HGMD; PMID: 10752524); Not observed at significant frequency in large population cohorts (gnomAD); 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: 32359821, 10752524, 31831576) |
| Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV001029935 | SCV001192731 | likely pathogenic | Autosomal dominant Alport syndrome | 2019-11-17 | no assertion criteria provided | clinical testing |