Submissions for variant NM_174936.4(PCSK9):c.45GCT[6] (p.Leu23del)

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000256266	SCV000323029	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Laboratory of Genetics and Molecular Cardiology, University of São Paulo	RCV000256266	SCV000588676	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Invitae	RCV000544697	SCV000644872	likely benign	Hypercholesterolemia, autosomal dominant, 3	2024-02-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000256266	SCV000690983	likely benign	Hypercholesterolemia, familial, 1	2017-07-07	criteria provided, single submitter	clinical testing
Robarts Research Institute, Western University	RCV000256266	SCV000782988	likely benign	Hypercholesterolemia, familial, 1	2018-01-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001194056	SCV001363304	benign	not specified	2019-08-13	criteria provided, single submitter	clinical testing	Variant summary: PCSK9 c.63_65delGCT (p.Leu23del) results in an in-frame deletion that is predicted to remove a Leu amino acid from the encoded protein. The variant allele was found at a frequency of 0.0007 in 161082 control chromosomes. The observed variant frequency is approximately 35-folds over the estimated maximal expected allele frequency for a pathogenic variant in PCSK9 causing Early Onset Coronary Artery Disease phenotype (2e-05), strongly suggesting that the variant is benign. Five ClinVar submissions (evaluation after 2014) cites the variant three times as likely benign and twice as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001194056	SCV001470595	benign	not specified	2020-03-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001577383	SCV001804745	likely benign	not provided	2020-12-07	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 33303402, 29572815)
Ambry Genetics	RCV002365273	SCV002656673	likely benign	Cardiovascular phenotype	2018-07-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
PreventionGenetics, part of Exact Sciences	RCV003977721	SCV004793510	likely benign	PCSK9-related condition	2019-06-04	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000256266	SCV000606672	benign	Hypercholesterolemia, familial, 1		no assertion criteria provided	research