Submissions for variant NM_000384.3(APOB):c.1785C>G (p.Ser595=)

gnomAD frequency: 0.00247  dbSNP: rs139864087

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001094649	SCV000427150	benign	Hypercholesterolemia, autosomal dominant, type B	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	RCV000278128	SCV000427151	likely benign	Familial hypobetalipoproteinemia 1	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001837876	SCV000659272	benign	Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1	2024-01-31	criteria provided, single submitter	clinical testing
Robarts Research Institute, Western University	RCV000398501	SCV000782825	likely benign	Hypercholesterolemia, familial, 1	2018-01-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000831715	SCV000973468	likely benign	not provided	2020-12-21	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000831715	SCV001133396	benign	not provided	2023-06-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002411227	SCV002714973	benign	Cardiovascular phenotype	2016-09-21	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	RCV000831715	SCV004564850	benign	not provided	2023-11-11	criteria provided, single submitter	clinical testing
GENinCode PLC	RCV004577522	SCV005061705	benign	Familial hypercholesterolemia	2024-06-19	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000831715	SCV005262646	likely benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV004530355	SCV004751818	benign	APOB-related disorder	2019-07-08	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).