Submissions for variant NM_000384.3(APOB):c.8462C>T (p.Pro2821Leu)

gnomAD frequency: 0.00267  dbSNP: rs72653095

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000202677	SCV000257688	uncertain significance	Hypercholesterolemia, familial, 1	2015-02-13	criteria provided, single submitter	clinical testing
Invitae	RCV001837756	SCV000284775	benign	Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1	2024-01-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000245691	SCV000303954	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094731	SCV000427013	likely benign	Hypercholesterolemia, autosomal dominant, type B	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000245691	SCV000538309	benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: High frequency
GeneDx	RCV000845531	SCV000730566	likely benign	not provided	2021-04-23	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22995991, 24503134, 20657596, 18710658, 19602640, 27884173, 27153395, 30526649)
Robarts Research Institute, Western University	RCV000202677	SCV000782884	likely benign	Hypercholesterolemia, familial, 1	2018-01-02	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000845531	SCV000987645	uncertain significance	not provided		criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000845531	SCV001133426	benign	not provided	2020-01-09	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000845531	SCV001152132	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	APOB: BP4, BS2
Illumina Laboratory Services, Illumina	RCV001142149	SCV001302559	uncertain significance	Familial hypobetalipoproteinemia 1	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Ambry Genetics	RCV002444821	SCV002676685	benign	Cardiovascular phenotype	2016-05-14	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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	RCV000845531	SCV004562840	likely benign	not provided	2023-09-08	criteria provided, single submitter	clinical testing