Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute Of Human Genetics Munich, |
RCV000021484 | SCV001149734 | pathogenic | X-linked Alport syndrome | 2019-05-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001035050 | SCV001198358 | likely pathogenic | not provided | 2022-01-05 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1069 of the COL4A5 protein (p.Gly1069Val). 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.Gly1069 amino acid residue in COL4A5. Other variant(s) that disrupt this residue have been observed in individuals with COL4A5-related conditions (PMID: 24304881), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 24605). This missense change has been observed in individuals with X-linked recessive COL4A5-related conditions (PMID: 20378821; Invitae). This variant is not present in population databases (gnomAD no frequency). |