Submissions for variant NM_000312.4(PROC):c.814C>T (p.Arg272Cys)

gnomAD frequency: 0.00004  dbSNP: rs121918154

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000852227	SCV000899949	likely pathogenic	Thromboembolism	2019-02-01	criteria provided, single submitter	research
Invitae	RCV000000706	SCV002145523	pathogenic	Thrombophilia due to protein C deficiency, autosomal dominant	2023-12-23	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 272 of the PROC protein (p.Arg272Cys). This variant is present in population databases (rs121918154, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of protein C deficiency type 1 (PMID: 1868249, 8093743, 22627591, 31064749). It has also been observed to segregate with disease in related individuals. This variant is also known as Arg230Cys. ClinVar contains an entry for this variant (Variation ID: 671). 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 PROC protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV000000706	SCV002500905	likely pathogenic	Thrombophilia due to protein C deficiency, autosomal dominant		criteria provided, single submitter	clinical testing
OMIM	RCV000000706	SCV000020856	pathogenic	Thrombophilia due to protein C deficiency, autosomal dominant	1993-01-16	no assertion criteria provided	literature only