ClinVar Miner

Submissions for variant NM_174936.3(PCSK9):c.385G>A (p.Asp129Asn)

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Total submissions: 5
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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 RCV000417258 SCV000503504 likely pathogenic Familial hypercholesterolemia 3 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 2, family members = 2, with co-segregation / Software predictions: Conflicting
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000497232 SCV000588680 benign Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Invitae RCV000417258 SCV000965292 likely pathogenic Familial hypercholesterolemia 3 2019-12-05 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 129 of the PCSK9 protein (p.Asp129Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs778738291, ExAC 0.002%). This variant has been observed in individuals affected with familial hypercholesterolemia (PMID: 23680767, 19081568, 23064986, 26374825, Invitae). ClinVar contains an entry for this variant (Variation ID: 375844). Experimental studies have reported conflicting results on whether this missense change results in a reduction in LDL-receptor protein (PMID: 19081568, 23064986, 26195630). The observation of one or more missense substitutions at this codon (p.Asp129Asn and p.Asp129Gly) in affected individuals suggests that this may be a clinically significant residue (PMID: 27280970, 17765244). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Color RCV001185722 SCV001351975 uncertain significance Familial hypercholesterolemia 2018-11-04 criteria provided, single submitter clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000497232 SCV000606689 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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