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

Total submissions: 10

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
Labcorp Genetics (formerly Invitae), Labcorp	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