Submissions for variant NM_174936.4(PCSK9):c.1327G>A (p.Ala443Thr)

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000241843	SCV000316564	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000309633	SCV000358254	benign	Hypobetalipoproteinemia	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000417327	SCV000358255	benign	Hypercholesterolemia, autosomal dominant, 3	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix	RCV000417327	SCV000503517	likely benign	Hypercholesterolemia, autosomal dominant, 3	2016-12-16	criteria provided, single submitter	clinical testing	subjects mutated among 2600 FH index cases screened = 8 / Software predictions: Benign
Labcorp Genetics (formerly Invitae), Labcorp	RCV000417327	SCV000555879	benign	Hypercholesterolemia, autosomal dominant, 3	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000759907	SCV000729976	benign	not provided	2019-06-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 16211558, 18680192, 23663650, 16909389, 29540175, 30899674, 29447211)
Robarts Research Institute, Western University	RCV000362210	SCV000782975	benign	Hypercholesterolemia, familial, 1	2018-01-02	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759907	SCV000889598	benign	not provided	2022-06-16	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771083	SCV000902626	benign	Familial hypercholesterolemia	2017-05-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002379093	SCV002690506	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000759907	SCV004564706	benign	not provided	2023-10-16	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000417327	SCV004842381	benign	Hypercholesterolemia, autosomal dominant, 3	2024-02-05	criteria provided, single submitter	clinical testing
Laboratory of Genetics and Molecular Cardiology, University of São Paulo	RCV000362210	SCV000588682	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	flagged submission	research
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000362210	SCV000606703	pathogenic	Hypercholesterolemia, familial, 1		flagged submission	research
Cohesion Phenomics	RCV000771083	SCV003836780	benign	Familial hypercholesterolemia	2023-02-09	no assertion criteria provided	clinical testing