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

dbSNP: rs1688692415

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001202927	SCV001374062	uncertain significance	Thrombophilia due to protein C deficiency, autosomal dominant	2024-10-31	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). 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%. 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