Submissions for variant NM_000384.3(APOB):c.11477C>T (p.Thr3826Met)

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001837767	SCV000284757	benign	Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1	2024-01-31	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000239211	SCV000296911	benign	Hypercholesterolemia, familial, 1	2015-07-29	criteria provided, single submitter	clinical testing
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000239211	SCV000322859	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research	0/190 non-FH alleles
Illumina Laboratory Services, Illumina	RCV001094759	SCV000426961	likely 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 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	RCV000293206	SCV000426962	uncertain significance	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, 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.
GeneDx	RCV000845395	SCV000521121	likely benign	not provided	2020-07-28	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function This variant is associated with the following publications: (PMID: 30270084, 26020417, 21502677, 27153395, 24503134)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000427612	SCV000538307	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: ExAC: 0.7% (84/11556) Latino chromosomes
Color Diagnostics, LLC DBA Color Health	RCV000239211	SCV000687192	likely benign	Hypercholesterolemia, familial, 1	2017-07-10	criteria provided, single submitter	clinical testing
Robarts Research Institute, Western University	RCV000239211	SCV000782796	uncertain significance	Hypercholesterolemia, familial, 1	2018-01-02	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000845395	SCV000987458	likely benign	not provided		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000845395	SCV001156206	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	APOB: BP4, BS2
Ambry Genetics	RCV002450669	SCV002613536	likely benign	Cardiovascular phenotype	2018-08-27	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000845395	SCV004220782	likely benign	not provided	2023-08-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003929938	SCV004743498	likely benign	APOB-related condition	2020-10-02	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Laboratory of Genetics and Molecular Cardiology, University of São Paulo	RCV000239211	SCV000588457	likely pathogenic	Hypercholesterolemia, familial, 1	2016-03-01	flagged submission	research