ClinVar Miner

Submissions for variant NM_000313.4(PROS1):c.1747A>C (p.Asn583His)

gnomAD frequency: 0.00014  dbSNP: rs139479630
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER _CC_NCGL, University of Washington RCV000148755 SCV000190492 uncertain significance Thrombophilia due to protein S deficiency, autosomal dominant 2014-06-01 criteria provided, single submitter research Low GERP score may suggest that this variant may belong in a lower pathogenicity class
Labcorp Genetics (formerly Invitae), Labcorp RCV001850018 SCV002186373 uncertain significance Thrombophilia due to protein S deficiency, autosomal recessive 2022-06-14 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 583 of the PROS1 protein (p.Asn583His). This variant is present in population databases (rs139479630, gnomAD 0.02%). This missense change has been observed in individual(s) with PROS1 deficiency (PMID: 15712227, 22627591). ClinVar contains an entry for this variant (Variation ID: 161349). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect PROS1 function (PMID: 15712227). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002478415 SCV002794267 uncertain significance Thrombophilia due to protein S deficiency, autosomal dominant; Thrombophilia due to protein S deficiency, autosomal recessive 2022-02-17 criteria provided, single submitter clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV004815209 SCV005068861 uncertain significance Retinal dystrophy 2022-01-01 criteria provided, single submitter clinical testing

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