ClinVar Miner

Submissions for variant NM_000312.4(PROC):c.541T>G (p.Phe181Val)

gnomAD frequency: 0.00005  dbSNP: rs199469470
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001927369 SCV002159697 pathogenic Thrombophilia due to protein C deficiency, autosomal dominant 2023-05-26 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PROC function (PMID: 17649706). 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) performed at Invitae indicates that this missense variant is not expected to disrupt PROC protein function. ClinVar contains an entry for this variant (Variation ID: 1394296). This variant is also known as F139V. This missense change has been observed in individuals with protein C deficiency (PMID: 8883262, 24103874, 24782131, 24911457, 25648792, 28111891). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs199469470, gnomAD 0.07%). This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 181 of the PROC protein (p.Phe181Val).
Fulgent Genetics, Fulgent Genetics RCV002503517 SCV002804523 likely pathogenic Thrombophilia due to protein C deficiency, autosomal recessive; Thrombophilia due to protein C deficiency, autosomal dominant 2021-07-27 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV004793578 SCV005413495 pathogenic not provided 2024-02-27 criteria provided, single submitter clinical testing PP1_strong, PM1_supporting, PM2_moderate, PM3_strong, PS3_supporting, PS4_moderate
Juno Genomics, Hangzhou Juno Genomics, Inc RCV002503517 SCV005417287 likely pathogenic Thrombophilia due to protein C deficiency, autosomal recessive; Thrombophilia due to protein C deficiency, autosomal dominant criteria provided, single submitter clinical testing PM2_Supporting+PP3+PM3_Strong+PS4_Supporting+PP4

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