ClinVar Miner

Submissions for variant NM_174936.3(PCSK9):c.616G>A (p.Glu206Lys) (rs753857795)

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Total submissions: 3
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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 RCV000417303 SCV000503505 likely benign Familial hypercholesterolemia 3 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1, family members = 4, without co-segregation / Software predictions: Benign
Invitae RCV000417303 SCV000932234 uncertain significance Familial hypercholesterolemia 3 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 206 of the PCSK9 protein (p.Glu206Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs753857795, ExAC 0.005%). This variant has been observed in an individual with clinical features of familial hypercholesterolemia (PMID: 23663650). ClinVar contains an entry for this variant (Variation ID: 375845). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Color RCV001189168 SCV001356400 uncertain significance Familial hypercholesterolemia 2020-03-02 criteria provided, single submitter clinical testing

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