Submissions for variant NM_174936.3(PCSK9):c.1773C>G (p.His591Gln) (rs529912877)

Total submissions: 3

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	RCV000417320	SCV000503514	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: Benign
Color	RCV000771326	SCV000903593	uncertain significance	Familial hypercholesterolemia	2018-06-06	criteria provided, single submitter	clinical testing	Variant of Uncertain Significance due to insufficient evidence: This variant is a missense variant located in the CM2 C-terminal domain of the PCSK9 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has the variant been reported in individuals affected with familial hypercholesterolemia in the literature. This variant is fairly common in the general population and has been identified in 31/28252 (0.11%) South Asian chromosomes by the Genome Aggregation Database (gnomAD). Although the relatively high frequency of this variant in the general population suggests that it is unlikely to be disease-causing, available evidence is insufficient to rule out the pathogenicity of this variant conclusively.
Invitae	RCV000862909	SCV001003477	benign	not provided	2018-08-13	criteria provided, single submitter	clinical testing