Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003565441 | SCV004317745 | likely pathogenic | not provided | 2023-08-15 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly475 amino acid residue in COL4A4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31934206). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 COL4A4 protein function. ClinVar contains an entry for this variant (Variation ID: 599080). This variant has not been reported in the literature in individuals affected with COL4A4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 475 of the COL4A4 protein (p.Gly475Val). |
| Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV000735674 | SCV000863817 | likely pathogenic | Autosomal dominant Alport syndrome | 2018-02-19 | no assertion criteria provided | clinical testing |