Submissions for variant NM_000312.4(PROC):c.1106C>T (p.Pro369Leu)

gnomAD frequency: 0.00001  dbSNP: rs1211098698

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001378201	SCV001575722	pathogenic	Thrombophilia due to protein C deficiency, autosomal dominant	2023-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 369 of the PROC protein (p.Pro369Leu). 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: 7792728, 23174622, 31254973). It has also been observed to segregate with disease in related individuals. This variant is also known as 8695C>T (Pro327Leu). ClinVar contains an entry for this variant (Variation ID: 1067044). 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. For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic	RCV001509161	SCV001715719	pathogenic	not provided	2024-08-13	criteria provided, single submitter	clinical testing	PP1_strong, PM1, PM2, PS4_moderate
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV001378201	SCV002500903	uncertain significance	Thrombophilia due to protein C deficiency, autosomal dominant		criteria provided, single submitter	clinical testing
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	RCV001378201	SCV005627698	likely pathogenic	Thrombophilia due to protein C deficiency, autosomal dominant	2024-01-18	criteria provided, single submitter	clinical testing
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV003333766	SCV004041769	pathogenic	Thrombophilia due to protein C deficiency, autosomal recessive	2023-10-09	no assertion criteria provided	clinical testing
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV001378201	SCV004101061	pathogenic	Thrombophilia due to protein C deficiency, autosomal dominant	2023-11-02	no assertion criteria provided	clinical testing