ClinVar Miner

Submissions for variant NM_000312.4(PROC):c.548G>T (p.Cys183Phe)

dbSNP: rs1284942525
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000645700 SCV000767451 likely pathogenic Thrombophilia due to protein C deficiency, autosomal dominant 2024-12-30 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 183 of the PROC protein (p.Cys183Phe). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individuals with protein C deficiency (PMID: 22627591; internal data). This variant is also known as Cys141Phe. ClinVar contains an entry for this variant (Variation ID: 536969). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PROC protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects PROC function (PMID: 22627591). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Illumina Laboratory Services, Illumina RCV000645700 SCV002540241 uncertain significance Thrombophilia due to protein C deficiency, autosomal dominant 2022-02-01 criteria provided, single submitter clinical testing The PROC c.548G>T (p.Cys183Phe) missense variant results in the substitution of cysteine at amino acid position 183 with phenylalanine. This variant has been reported in a heterozygous state in one individual with protein C deficiency with a measured protein C activity of 51% of normal (Caspers et al. 2012). The c.548G>T variant is reported in the Genome Aggregation Database in one allele at a frequency of 0.000009 in the European (non-Finnish) population (version 2.1.1). Based on the available evidence, the c.548G>T (p.Cys183Phe) variant is classified as a variant of uncertain significance for protein C deficiency.

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