Submissions for variant NM_000312.4(PROC):c.445dup (p.His149fs)

gnomAD frequency: 0.00001  dbSNP: rs772629538

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001898011	SCV002159871	pathogenic	Thrombophilia due to protein C deficiency, autosomal dominant	2024-01-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.His149Profs*13) in the PROC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PROC are known to be pathogenic (PMID: 17152060). This variant is present in population databases (rs772629538, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with protein C deficiency (PMID: 7913773). It has also been observed to segregate with disease in related individuals. This variant is also known as p.His107Profs and PC Vermont IIb. ClinVar contains an entry for this variant (Variation ID: 1389677). For these reasons, this variant has been classified as Pathogenic.
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota	RCV001898011	SCV004028487	pathogenic	Thrombophilia due to protein C deficiency, autosomal dominant	2023-07-05	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV004793573	SCV005413494	pathogenic	not provided	2024-02-19	criteria provided, single submitter	clinical testing	PP1_strong, PM2_moderate, PS4_moderate, PVS1