Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Diagnostics Division, |
RCV000993765 | SCV001142277 | uncertain significance | Steroid-resistant nephrotic syndrome | 2019-08-17 | criteria provided, single submitter | research | The de novo variant Pro986Ser identified in our 18 months old girl with the steroid resistant nephrotic syndrome is absent in population databases such as the 1000genomes, ExAC and gnomAD, etc. Several studies have reported that the high content of the proline residues are critical for the structure stability and the function of the collagen structure (Krane, S. M.2008, Myllyharju and Kivirikko 2004). Hence, based on the the absence of this variant in the population databases and the previous studies demonstrating the critical role of the Proline for the collagen structure and function can qualify the criteria of Pro986Ser variant to be clinically significant. |
Invitae | RCV002304222 | SCV002592409 | uncertain significance | not provided | 2022-07-20 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 805943). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 986 of the COL4A4 protein (p.Pro986Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL4A4-related conditions. 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 not expected to disrupt COL4A4 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. |