Submissions for variant NM_174936.4(PCSK9):c.336G>A (p.Leu112=)

gnomAD frequency: 0.00033  dbSNP: rs79805678

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000469585	SCV000555878	benign	Hypercholesterolemia, autosomal dominant, 3	2025-01-23	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000582082	SCV000690980	benign	Hypercholesterolemia, familial, 1	2017-10-16	criteria provided, single submitter	clinical testing
Robarts Research Institute, Western University	RCV000582082	SCV000782986	benign	Hypercholesterolemia, familial, 1	2018-01-02	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001101139	SCV001257719	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000469585	SCV001257720	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001778968	SCV002015108	benign	not specified	2021-10-02	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001778968	SCV002047052	benign	not specified	2021-05-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002451154	SCV002615527	likely benign	Cardiovascular phenotype	2015-03-23	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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	RCV000469585	SCV004839893	benign	Hypercholesterolemia, autosomal dominant, 3	2024-02-05	criteria provided, single submitter	clinical testing
GENinCode PLC	RCV004586722	SCV005077868	benign	Familial hypercholesterolemia	2023-12-21	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV004711117	SCV005257974	likely benign	not provided		criteria provided, single submitter	not provided