Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000689216 | SCV000816856 | likely pathogenic | Thrombophilia due to protein C deficiency, autosomal dominant | 2022-02-17 | criteria provided, single submitter | clinical testing | 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.Gly324 amino acid residue in PROC. Other variant(s) that disrupt this residue have been observed in individuals with PROC-related conditions (PMID: 7792728), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 568761). This variant is also known as G282S. This missense change has been observed in individual(s) with clinical features of protein C deficiency (PMID: 7831652, 27517348; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs571278160, gnomAD 0.06%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 324 of the PROC protein (p.Gly324Ser). |