ClinVar Miner

Submissions for variant NM_174936.4(PCSK9):c.1856A>C (p.Gln619Pro)

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Total submissions: 10
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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 RCV000417232 SCV000503518 likely benign Hypercholesterolemia, autosomal dominant, 3 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1 / Software predictions: Benign
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000497196 SCV000588688 uncertain significance Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research
Invitae RCV000417232 SCV000644865 benign Hypercholesterolemia, autosomal dominant, 3 2024-01-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590727 SCV000699988 benign not provided 2016-04-28 criteria provided, single submitter clinical testing Variant summary: The PCSK9 c.1856A>C variant affects a non-conserved nucleotide, resulting in amino acid change from Gln to Pro. 3/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). This variant was found in 101/54678 control chromosomes at a frequency of 0.0018472, which is about 99 times the maximal expected frequency of a pathogenic PCSK9 allele (0.0000188), suggesting this variant is benign. This variant has been found only in Africans, including African controls (101/5202 ExAC African chromosomes) and both high and low LDL African patients in the literature, at a similar allele frequency (1.5-2%). Taken together, based on the prevalence of this variant in general population, this variant was classified as Benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590727 SCV000889600 benign not provided 2018-08-23 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000776087 SCV000910853 benign Familial hypercholesterolemia 2018-01-24 criteria provided, single submitter clinical testing
GeneDx RCV000590727 SCV001915167 likely benign not provided 2021-05-27 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 16465619, 17971861)
Ambry Genetics RCV002411284 SCV002722111 benign Cardiovascular phenotype 2016-03-23 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
All of Us Research Program, National Institutes of Health RCV000417232 SCV004844476 benign Hypercholesterolemia, autosomal dominant, 3 2024-02-05 criteria provided, single submitter clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000497196 SCV000606714 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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