ClinVar Miner

Submissions for variant NM_000313.4(PROS1):c.601+1G>A

dbSNP: rs1708665916
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 RCV001036048 SCV001199395 likely pathogenic Thrombophilia due to protein S deficiency, autosomal recessive 2023-03-25 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. ClinVar contains an entry for this variant (Variation ID: 835217). This sequence change affects a donor splice site in intron 6 of the PROS1 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 PROS1 are known to be pathogenic (PMID: 9241758). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with protein S deficiency (PMID: 26046366).
New York Genome Center RCV003448362 SCV004176044 likely pathogenic Thrombophilia due to protein S deficiency, autosomal dominant; Thrombophilia due to protein S deficiency, autosomal recessive 2023-05-25 criteria provided, single submitter clinical testing The inherited c.601+1G>A variant identified in the PROS1 gene is a canonical splice donor variant within intron 6/14, and is expected to lead to the loss of the splice donor (SpliceAI=0.81, donor loss). This variant is absent from population databases (gnomAD v2.1.1, gnomADv3.1.2, BRAVO-TOPMed, All of Us) suggesting it is not a common benign variant in the populations represented in those databases. This variant is reported in ClinVar as Likely Pathogenic [VarID:835217] and has been reported in one individual with Protein S deficiency in the literature [PMID:26046366] who was reported to have mildly low protein S activity (Supplementary Table S2; PMID:26046366). Given the available evidence, the inherited c.601+1G>A variant identified in the PROS1 gene is reported 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.