Submissions for variant NM_000384.3(APOB):c.12794T>C (p.Val4265Ala)

gnomAD frequency: 0.00516  dbSNP: rs61743502

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001837770	SCV000284760	benign	Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000758755	SCV000729915	likely benign	not provided	2020-11-05	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30270084, 18710658, 26415676, 27153395, 33111339)
Robarts Research Institute, Western University	RCV000584100	SCV000782809	benign	Hypercholesterolemia, familial, 1	2018-01-02	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000758755	SCV000887570	benign	not provided	2022-06-12	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771081	SCV000902619	likely benign	Familial hypercholesterolemia	2018-06-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000758755	SCV001152106	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	APOB: BP4, BS2
Illumina Laboratory Services, Illumina	RCV001138999	SCV001299102	uncertain significance	Familial hypobetalipoproteinemia 1	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, 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.
Illumina Laboratory Services, Illumina	RCV001139000	SCV001299103	likely benign	Hypercholesterolemia, autosomal dominant, type B	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.
Ambry Genetics	RCV002372257	SCV002686008	likely benign	Cardiovascular phenotype	2018-05-21	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000758755	SCV004564027	likely benign	not provided	2023-08-28	criteria provided, single submitter	clinical testing
GENinCode PLC	RCV000771081	SCV005074095	benign	Familial hypercholesterolemia	2022-11-14	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000758755	SCV001740848	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000606261	SCV001925553	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000758755	SCV001967398	likely benign	not provided		no assertion criteria provided	clinical testing