ClinVar Miner

Submissions for variant NM_000312.4(PROC):c.400+1G>A

dbSNP: rs1189377845
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000818570 SCV000959190 pathogenic Thrombophilia due to protein C deficiency, autosomal dominant 2024-02-27 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 5 of the PROC gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PROC are known to be pathogenic (PMID: 17152060). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with protein C deficiency (PMID: 9840027, 22627591). ClinVar contains an entry for this variant (Variation ID: 661205). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.