Submissions for variant NM_000312.4(PROC):c.659G>C (p.Arg220Pro)

dbSNP: rs121918153

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003093959	SCV003524949	uncertain significance	Thrombophilia due to protein C deficiency, autosomal dominant	2022-02-11	criteria provided, single submitter	clinical testing	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. This variant disrupts the p.Arg220 amino acid residue in PROC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1301954, 1301959, 1511989, 7605880, 8499565, 18954896, 31254973). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is also known as Arg178Pro. This missense change has been observed in individuals with protein C deficiency (PMID: 7605880; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 220 of the PROC protein (p.Arg220Pro).
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002245355	SCV002515551	likely pathogenic	Reduced protein C activity		no assertion criteria provided	research