Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000778563 | SCV000914865 | uncertain significance | Thrombophilia due to protein C deficiency, autosomal dominant | 2018-11-15 | criteria provided, single submitter | clinical testing | The PROC c.629C>T (p.Pro210Leu) missense variant has been reported in four studies and is found in a total of 12 individuals with protein C deficiency including two in a homozygous state, one in a compound heterozygous state, and at least nine in a heterozygous state (Conard et al. 1992; Reitsma et al. 1995; David et al. 2011; Kim et al. 2014). One homozygous patient had at least six unaffected family members who carried the variant in a heterozygous state (Conard et al. 1992). Control data are unavailable for this variant, which is reported at a frequency of 0.00002 in the European (non-Finnish) population of the Exome Aggregation Consortium, but this is based on one allele only so the variant is presumed to be rare. Based on the evidence, the p.Pro210Leu variant is classified as a variant of unknown significance but suspicious of pathogenicity for protein C deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Invitae | RCV000778563 | SCV002243051 | pathogenic | Thrombophilia due to protein C deficiency, autosomal dominant | 2021-03-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with protein C deficiency (PMID: 1347608, 18573519, 21621249, 7482420, 31254973). It has also been observed to segregate with disease in related individuals. This variant is also known as 6216C>T; Pro168Leu in the literature. ClinVar contains an entry for this variant (Variation ID: 661). This variant is present in population databases (rs121918145, ExAC 0.002%). This sequence change replaces proline with leucine at codon 210 of the PROC protein (p.Pro210Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. |
| OMIM | RCV000000696 | SCV000020846 | pathogenic | Thrombophilia due to protein C deficiency, autosomal recessive | 1992-03-21 | no assertion criteria provided | literature only |