ClinVar Miner

Submissions for variant NM_000312.4(PROC):c.524G>A (p.Cys175Tyr)

gnomAD frequency: 0.00001  dbSNP: rs199469474
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852149 SCV000899789 likely pathogenic Reduced protein C activity 2019-02-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV003495184 SCV004293369 uncertain significance Thrombophilia due to protein C deficiency, autosomal dominant 2023-08-04 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.Cys175 amino acid residue in PROC. Other variant(s) that disrupt this residue have been observed in individuals with PROC-related conditions (PMID: 28607330), which suggests that this may be a clinically significant amino acid residue. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PROC protein function. ClinVar contains an entry for this variant (Variation ID: 627327). This missense change has been observed in individuals with protein C deficiency (PMID: 22545135, 22627591, 24028705, 31064749; Invitae). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 175 of the PROC protein (p.Cys175Tyr).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.