Submissions for variant NM_174936.4(PCSK9):c.137G>T (p.Arg46Leu)

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000203182	SCV000258263	benign	Hypercholesterolemia, autosomal dominant, 3	2015-06-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000203182	SCV000291595	benign	Hypercholesterolemia, autosomal dominant, 3	2024-01-31	criteria provided, single submitter	clinical testing
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000256313	SCV000323030	benign	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research	3/100 normolipidemic controls; 0/100 normolipidemic individuals
Illumina Laboratory Services, Illumina	RCV000203182	SCV000358213	likely benign	Hypercholesterolemia, autosomal dominant, 3	2018-03-06	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Robarts Research Institute, Western University	RCV000256313	SCV000484817	benign	Hypercholesterolemia, familial, 1	2019-08-22	criteria provided, single submitter	clinical testing
Laboratory of Genetics and Molecular Cardiology, University of São Paulo	RCV000256313	SCV000588678	benign	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Fundacion Hipercolesterolemia Familiar	RCV000256313	SCV000607712	benign	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Color Diagnostics, LLC DBA Color Health	RCV001523785	SCV000690958	benign	Familial hypercholesterolemia	2020-12-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000605465	SCV000730049	benign	not specified	2017-05-08	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985896	SCV001134562	benign	not provided	2023-01-06	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001099060	SCV001255475	benign	Hypobetalipoproteinemia	2018-03-06	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000985896	SCV002505975	benign	not provided	2023-09-08	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002381236	SCV002696724	benign	Cardiovascular phenotype	2017-03-16	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.
Fulgent Genetics, Fulgent Genetics	RCV000203182	SCV002798957	benign	Hypercholesterolemia, autosomal dominant, 3	2022-04-28	criteria provided, single submitter	clinical testing
GENinCode PLC	RCV001523785	SCV005077864	benign	Familial hypercholesterolemia	2022-07-01	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000985896	SCV005257970	likely benign	not provided		criteria provided, single submitter	not provided
OMIM	RCV000003012	SCV000023170	association	Low density lipoprotein cholesterol level quantitative trait locus 1	2008-03-20	no assertion criteria provided	literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000508774	SCV000606676	pathogenic	Hypocholesterolemia		no assertion criteria provided	research