Submissions for variant NM_174936.4(PCSK9):c.1026A>G (p.Gln342=)

gnomAD frequency: 0.98223  dbSNP: rs509504

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000249882	SCV000316563	benign	not specified		criteria provided, single submitter	clinical testing
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000256296	SCV000323061	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Illumina Laboratory Services, Illumina	RCV000337265	SCV000358246	benign	Hypobetalipoproteinemia	2018-01-12	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	RCV000610611	SCV000358247	benign	Hypercholesterolemia, autosomal dominant, 3	2018-01-12	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.
GeneDx	RCV000249882	SCV000519559	benign	not specified	2016-09-30	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.
Color Diagnostics, LLC DBA Color Health	RCV000256296	SCV000690954	benign	Hypercholesterolemia, familial, 1	2017-06-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000610611	SCV001720523	benign	Hypercholesterolemia, autosomal dominant, 3	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000610611	SCV002029469	benign	Hypercholesterolemia, autosomal dominant, 3	2021-09-05	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001812749	SCV002047712	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002379092	SCV002689960	benign	Cardiovascular phenotype	2015-12-08	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	RCV000610611	SCV004836419	benign	Hypercholesterolemia, autosomal dominant, 3	2024-02-05	criteria provided, single submitter	clinical testing
GENinCode PLC	RCV003148698	SCV005062048	benign	Familial hypercholesterolemia	2022-07-01	criteria provided, single submitter	clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000256296	SCV000606697	benign	Hypercholesterolemia, familial, 1		no assertion criteria provided	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000610611	SCV000734043	benign	Hypercholesterolemia, autosomal dominant, 3		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000249882	SCV001921290	benign	not specified		no assertion criteria provided	clinical testing
Cohesion Phenomics	RCV003148698	SCV003836779	benign	Familial hypercholesterolemia	2023-02-09	no assertion criteria provided	clinical testing