Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002016059 | SCV002299391 | likely pathogenic | not provided | 2021-06-14 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with X-linked Alport syndrome (PMID: 26809805). ClinVar contains an entry for this variant (Variation ID: 587218). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 1632 of the COL4A5 protein (p.Cys1632Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. 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. 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.Cys1632 ‚Äãamino acid residue in COL4A5. Other variant(s) that disrupt this residue have been observed in individuals with COL4A5-related conditions (PMID: 20378821, 24033287, 26809805), which suggests that this may be a clinically significant amino acid residue |