Submissions for variant NM_000384.3(APOB):c.2630C>T (p.Pro877Leu)

gnomAD frequency: 0.00063  dbSNP: rs12714097

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001838000	SCV000777095	likely benign	Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1	2024-01-19	criteria provided, single submitter	clinical testing
Robarts Research Institute, Western University	RCV000582805	SCV000782831	likely benign	Hypercholesterolemia, familial, 1	2018-01-02	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000845557	SCV000987686	uncertain significance	not provided		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000845557	SCV001152167	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	APOB: BP4
Illumina Laboratory Services, Illumina	RCV001138483	SCV001298540	uncertain significance	Familial hypobetalipoproteinemia 1	2018-05-01	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001138484	SCV001298541	uncertain significance	Hypercholesterolemia, autosomal dominant, type B	2018-05-01	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001138483	SCV001367850	uncertain significance	Familial hypobetalipoproteinemia 1	2019-03-12	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001138484	SCV001429235	uncertain significance	Hypercholesterolemia, autosomal dominant, type B	2021-09-21	criteria provided, single submitter	clinical testing
Genetics and Molecular Pathology, SA Pathology	RCV001138484	SCV002556621	uncertain significance	Hypercholesterolemia, autosomal dominant, type B	2020-05-05	criteria provided, single submitter	clinical testing	The APOB c.2630C>T variant is classified as VUS (BS1) Population frequency too high for APOB with respect to FH (only accounts for 1-5% of FH cases). Conflicting in silico data, no functional evidence.
Ambry Genetics	RCV002431732	SCV002743261	likely benign	Cardiovascular phenotype	2022-07-13	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.