ClinVar Miner

Submissions for variant NM_000313.4(PROS1):c.1351C>T (p.Arg451Ter)

dbSNP: rs5017717
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599381 SCV000710003 pathogenic not provided 2018-02-19 criteria provided, single submitter clinical testing The R451X variant in the PROS1 gene has been reported previously in multiple unrelated individuals with protein S deficiency (Mustafa et al., 1995; Klostermeier et al., 2015; Tang et al., 2013; Bruwer et al., 2016; Biguzzi et al., 2005). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R451X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R451X as a pathogenic variant,
NIHR Bioresource Rare Diseases, University of Cambridge RCV000851685 SCV000899485 likely pathogenic Protein S deficiency disease 2019-02-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001204662 SCV001375878 pathogenic Thrombophilia due to protein S deficiency, autosomal recessive 2024-04-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg451*) in the PROS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PROS1 are known to be pathogenic (PMID: 9241758). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with protein S deficiency (PMID: 7579449, 18322254, 29321366). It has also been observed to segregate with disease in related individuals. This variant is also known as Arg410STOP. ClinVar contains an entry for this variant (Variation ID: 503726). For these reasons, this variant has been classified as Pathogenic.
Provincial Medical Genetics Program of British Columbia, University of British Columbia RCV002062111 SCV002320842 pathogenic Thrombophilia due to protein S deficiency, autosomal dominant 2022-01-01 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV002062111 SCV002579504 pathogenic Thrombophilia due to protein S deficiency, autosomal dominant 2021-09-08 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000599381 SCV005413594 pathogenic not provided 2024-04-11 criteria provided, single submitter clinical testing PP1_strong, PM2_moderate, PM3, PS3_moderate, PS4_moderate, PVS1
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas RCV002062111 SCV004101103 pathogenic Thrombophilia due to protein S deficiency, autosomal dominant 2023-11-02 no assertion criteria provided clinical testing

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