Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001964405 | SCV002253418 | likely pathogenic | not provided | 2021-03-15 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 464 of the COL4A3 protein (p.Gly464Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant has been observed in individual(s) with clinical features of Alport syndrome (Invitae). 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. This variant disrupts the p.Gly464 amino acid residue in COL4A3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14582039). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Fulgent Genetics, |
RCV002492185 | SCV002785288 | likely pathogenic | Autosomal dominant Alport syndrome; Autosomal recessive Alport syndrome; Benign familial hematuria | 2021-09-29 | criteria provided, single submitter | clinical testing |