ClinVar Miner

Submissions for variant NM_174936.3(PCSK9):c.835C>A (p.Pro279Thr) (rs72646509)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000417269 SCV000503507 uncertain significance Familial hypercholesterolemia 3 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1 / Software predictions: Damaging
Invitae RCV000588730 SCV000644874 likely benign not provided 2018-07-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588730 SCV000700004 benign not provided 2017-05-22 criteria provided, single submitter clinical testing Variant summary: The PCSK9 c.835C>A (p.Pro279Thr) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 41/94810 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.004103 (31/7556). This frequency is about 205 times the estimated maximal expected allele frequency of a pathogenic PCSK9 variant (0.00002), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. The variant has been reported in the literature as a SNP and has been observed at equal frequencies both in patients with low LDL-C and high LDL-C. Therefore, its role in the pathophysiology of Familial Hypercholesterolemia and early onset CAD is suspect. One clinical diagnostic laboratory classified this variant as uncertain significance. Taken together, due to the relatively high frequency of the variant in the control population, this variant has been classified as benign.
Color RCV000776497 SCV000912079 likely benign Familial hypercholesterolemia 2018-04-02 criteria provided, single submitter clinical testing

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