Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000818570 | SCV000959190 | pathogenic | Thrombophilia due to protein C deficiency, autosomal dominant | 2018-11-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PROC are known to be pathogenic (PMID: 17152060). Disruption of this splice site has been observed in individuals affected with protein C deficiency (PMID: 9840027, 22627591). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change affects a donor splice site in intron 5 of the PROC gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
Prevention |
RCV004731041 | SCV005337639 | likely pathogenic | PROC-related disorder | 2024-05-23 | no assertion criteria provided | clinical testing | The PROC c.400+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge this variant has not been reported in literature. This variant has not been reported in a large population database, indicating this variant is rare. Variants that disrupt the consensus splice donor site in PROC are expected to be pathogenic. This variant is interpreted as likely pathogenic. |