Submissions for variant NM_000312.4(PROC):c.580C>T (p.Arg194Cys)

gnomAD frequency: 0.00004  dbSNP: rs371071104

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000148745	SCV000284567	uncertain significance	Thrombophilia due to protein C deficiency, autosomal dominant	2021-08-13	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with cysteine at codon 194 of the PROC protein (p.Arg194Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs371071104, ExAC 0.009%). This missense change has been observed in individuals with protein C deficiency (PMID: 7482420, 27517348). 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 disruptive. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on PROC function (PMID: 27517348). 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.
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV001270053	SCV001448787	uncertain significance	Thrombophilia due to protein C deficiency, autosomal recessive	2019-03-04	criteria provided, single submitter	clinical testing
CSER _CC_NCGL, University of Washington	RCV000148745	SCV000190482	uncertain significance	Thrombophilia due to protein C deficiency, autosomal dominant	2014-06-01	no assertion criteria provided	research