Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mayo Clinic Laboratories, |
RCV001507528 | SCV001713128 | likely pathogenic | not provided | 2019-10-06 | criteria provided, single submitter | clinical testing | PS4_moderate, PM2, PM5, PP3 |
Labcorp Genetics |
RCV001507528 | SCV005834774 | uncertain significance | not provided | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 157 of the CD46 protein (p.Cys157Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of atypical hemolytic uremic syndrome (PMID: 27268256). ClinVar contains an entry for this variant (Variation ID: 1162903). 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 CD46 protein function with a positive predictive value of 80%. 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. |