Submissions for variant NM_000312.4(PROC):c.791G>A (p.Arg264Lys)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV005198170	SCV005834831	uncertain significance	Thrombophilia due to protein C deficiency, autosomal dominant	2024-12-10	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 264 of the PROC protein (p.Arg264Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with pulmonary embolism (PMID: 28174134). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PROC protein function with a negative predictive value of 80%. This variant disrupts the p.Arg264 amino acid residue in PROC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24162787; internal data). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.