Submissions for variant NM_000384.3(APOB):c.3427C>T (p.Pro1143Ser)

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001837776	SCV000284767	likely benign	Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1	2024-02-01	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000456004	SCV000538327	uncertain significance	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: 1 paper, no segs, ExAC: 0.2% European chromosomes
Laboratory of Genetics and Molecular Cardiology, University of São Paulo	RCV000497223	SCV000588428	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Robarts Research Institute, Western University	RCV000497223	SCV000782842	uncertain significance	Hypercholesterolemia, familial, 1	2018-01-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771109	SCV000902802	likely benign	Familial hypercholesterolemia	2018-05-09	criteria provided, single submitter	clinical testing	Likely Benign based on current evidence: This variant (also known as p.Pro1116Ser in the mature protein) is a missense variant located in the beta 1 domain of the APOB protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in a Norwegian individual with hypercholesterolemia (PMID: 18710658) but it has also been identified in 464/277174 chromosomes (0.17%) in the general population by the Genome Aggregation Database (gnomAD). This variant allele frequency is greater than expected for the disorder based on prevalence, penetrance, and genetic heterogeneity. Based on available evidence, this variant is classified as Likely Benign.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000845457	SCV000987546	likely benign	not provided		criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000845457	SCV001133406	likely benign	not provided	2022-10-04	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000845457	SCV001250292	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	APOB: BP4
Illumina Laboratory Services, Illumina	RCV001137957	SCV001297956	uncertain significance	Hypercholesterolemia, autosomal dominant, type B	2017-04-27	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.
GeneDx	RCV000845457	SCV001802165	likely benign	not provided	2019-07-23	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22256951, 18710658)
Institute of Human Genetics, University Hospital Muenster	RCV002227096	SCV002506426	uncertain significance	Transient hyperlipidemia	2021-12-21	criteria provided, single submitter	clinical testing	ACMG categories: BS2
Ambry Genetics	RCV002450671	SCV002614493	likely benign	Cardiovascular phenotype	2019-01-04	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.
PreventionGenetics, part of Exact Sciences	RCV003401169	SCV004104178	uncertain significance	APOB-related condition	2023-03-25	criteria provided, single submitter	clinical testing	The APOB c.3427C>T variant is predicted to result in the amino acid substitution p.Pro1143Ser. This variant has been reported in individuals with hypercholesterolemia or high HDL-C level (Leren et al. 2008. PubMed ID: 18710658; Motazacker et al. 2013. PubMed ID: 23685560. Table SIV). This variant is reported in 0.28% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-21238323-G-A). In Clinvar, this variant has conflicting interpretations of likely benign and uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/237744/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Clinical Genetics, Academic Medical Center	RCV000456004	SCV001924063	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000845457	SCV001975473	likely benign	not provided		no assertion criteria provided	clinical testing