Submissions for variant NM_000384.3(APOB):c.7285T>A (p.Ser2429Thr)

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000203158	SCV000257685	uncertain significance	Hypercholesterolemia, familial, 1	2015-03-06	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224080	SCV000281157	uncertain significance	not provided	2016-04-18	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000456013	SCV000538324	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: Few reports, no segs, ExAC: 0.1% (92/66598) European chromosomes
Labcorp Genetics (formerly Invitae), Labcorp	RCV001837754	SCV000554822	likely benign	Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1	2024-01-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000224080	SCV000582163	uncertain significance	not provided	2021-11-23	criteria provided, single submitter	clinical testing	Identified in at least one individual with hypertriglyceridemia and possible FH in published literature (Johansen et al., 2010; Radovica-Spalvine et al., 2015); Identified in two unrelated families with FH, who also harbored other FH-related variants that were suspected to cause disease (Rabacchi et al., 2016; Alnouri et al., 20018); In one family, three individuals who were heterozygous for the S2429T variant in the APOB gene in addition to at least one pathogenic variant in the LDLR gene had lower LDL-C levels than family members who did not harbor the S2429T variant, leading the authors to hypothesize that the S2429T variant may have an LDL-lowering effect (Rabacchi et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar (ClinVar Variant ID#218448; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 33069457, 20657596, 26415676, 27578127, 27153395, 30270081)
Laboratory of Genetics and Molecular Cardiology, University of São Paulo	RCV000203158	SCV000588443	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Genetic Services Laboratory, University of Chicago	RCV000456013	SCV000593266	uncertain significance	not specified	2016-10-20	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771126	SCV000902877	likely benign	Familial hypercholesterolemia	2018-03-26	criteria provided, single submitter	clinical testing	Likely Benign based on current evidence: This missense variant (also known as p.Ser2402Thr in the mature protein) is located in the alpha 2 domain of the APOB protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on 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 Latvian individual with suspected hypercholesterolemia (PMID: 26415676). In an Italian family with hypercholesterolemia caused by biallelic LDLR mutations, this variant was suggested to have LDL-C lowering effect (PMID: 27578127). This variant has been identified in 136/126166 non-Finnish European chromosomes (0.11%) and 39/10136 Ashkenazi Jewish chromosomes (0.38%) 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	RCV000224080	SCV000987694	uncertain significance	not provided		criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000224080	SCV001133417	likely benign	not provided	2023-04-26	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000224080	SCV001152140	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	APOB: BP4
Illumina Laboratory Services, Illumina	RCV001139737	SCV001299918	uncertain significance	Hypercholesterolemia, autosomal dominant, type B	2019-09-09	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	RCV001139738	SCV001299919	uncertain significance	Familial hypobetalipoproteinemia 1	2019-09-09	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.
Ambry Genetics	RCV002381696	SCV002672551	likely benign	Cardiovascular phenotype	2019-01-14	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.
CSER _CC_NCGL, University of Washington	RCV000417323	SCV000503553	uncertain significance	Hypercholesterolemia	2016-08-01	no assertion criteria provided	research	Found in patient having exome sequencing for an unrelated indication. No known history hypercholesterolemia.
Clinical Genetics, Academic Medical Center	RCV000456013	SCV001922619	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000224080	SCV001966074	likely benign	not provided		no assertion criteria provided	clinical testing
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV001139737	SCV004099430	uncertain significance	Hypercholesterolemia, autosomal dominant, type B	2023-10-30	no assertion criteria provided	clinical testing