ClinVar Miner

Submissions for variant NM_000312.4(PROC):c.1155G>A (p.Met385Ile)

dbSNP: rs1688692415
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001202927 SCV001374062 uncertain significance Thrombophilia due to protein C deficiency, autosomal dominant 2023-12-02 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 385 of the PROC protein (p.Met385Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of PROC-related conditions (PMID: 8499565, 34650936). This variant is also known as Met343Ile. ClinVar contains an entry for this variant (Variation ID: 934521). 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 expected to disrupt PROC protein function with a positive predictive value of 80%. 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.
MGZ Medical Genetics Center RCV001202927 SCV002581253 likely pathogenic Thrombophilia due to protein C deficiency, autosomal dominant 2021-12-27 criteria provided, single submitter clinical testing
GeneDx RCV003313189 SCV004012245 uncertain significance not provided 2023-01-06 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as p.M343I; This variant is associated with the following publications: (PMID: 34650936, 8499565)
Mayo Clinic Laboratories, Mayo Clinic RCV003313189 SCV004226508 likely pathogenic not provided 2022-02-02 criteria provided, single submitter clinical testing PP3, PM1, PM2, PS4_moderate
CeGaT Center for Human Genetics Tuebingen RCV003313189 SCV005042523 likely pathogenic not provided 2024-04-01 criteria provided, single submitter clinical testing PROC: PM1, PM2, PS4:Moderate

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