Submissions for variant NM_000312.4(PROC):c.1042C>T (p.Arg348Ter)

dbSNP: rs121918141

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000000690	SCV003524951	pathogenic	Thrombophilia due to protein C deficiency, autosomal dominant	2022-01-11	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PROC protein in which other variant(s) (p.Pro405Alafs*20) have been determined to be pathogenic (PMID: 7670104, 25039884, 29356699). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 656). This premature translational stop signal has been observed in individual(s) with autosomal dominant protein C deficiency and autosomal recessive purpura fulminans (PMID: 2437584, 24122877, 26250584, 28607330). This variant is present in population databases (rs121918141, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg348*) in the PROC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 114 amino acid(s) of the PROC protein.
OMIM	RCV000000690	SCV000020840	pathogenic	Thrombophilia due to protein C deficiency, autosomal dominant	1992-08-01	no assertion criteria provided	literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528453	SCV001740235	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001528453	SCV001956208	pathogenic	not provided		no assertion criteria provided	clinical testing