ClinVar Miner

Submissions for variant NM_174936.3(PCSK9):c.323T>G (p.Leu108Arg) (rs1057519691)

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Total submissions: 2
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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 RCV000417273 SCV000503513 pathogenic Familial hypercholesterolemia 3 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1, family member = 1 / functionnal testing (PMID:22683120) / Software predictions: Benign
Integrated Genetics/Laboratory Corporation of America RCV000587518 SCV000699992 likely pathogenic Familial hypercholesterolemia 2017-02-23 criteria provided, single submitter clinical testing Variant summary: The PCSK9 c.323T>G (p.Leu108Arg) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant. This variant is absent in 121160 control chromosomes. This variant has been reported in one FH family with unequivocal co-segregation evidence (found in 4 affected members, not found in 3 unaffected members). In vitro study showed that p.L108R had a clear and significant gain-of-function effect. Taken together, this variant is classified as likely pathogenic until additional FH families are reported to carry this variant.

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