ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.11303T>C (p.Ile3768Thr)

gnomAD frequency: 0.00004  dbSNP: rs376825639
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001139320 SCV001299455 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). 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 RCV001139321 SCV001299456 uncertain significance Familial hypobetalipoproteinemia 1 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). 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.
Invitae RCV001856115 SCV002309602 likely benign Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 2023-11-25 criteria provided, single submitter clinical testing
AiLife Diagnostics, AiLife Diagnostics RCV001311548 SCV002501368 uncertain significance not provided 2021-04-27 criteria provided, single submitter clinical testing
New York Genome Center RCV001856115 SCV002764576 uncertain significance Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 2022-10-26 criteria provided, single submitter clinical testing The c.11303T>C p.(Ile3768Thr) variant identified in the APOB gene substitutes a moderately conserved Isoleucine for Threonine atamino acid 3768/4564 (exon 26/29). This variant is found with low frequency in population databases (gnomAD, BRAVO-TOPMed, All of Us) with highest allele frequency of 9.8e-5 (0 homozygotes; BRAVO-TOPMed) suggesting it is not a common benign variant in the populations represented in those databases. In silico algorithms predict this variant to be Neutral (REVEL:0.268) to the function of the canonical transcript. This variant is reported in ClinVar as a Variant of UncertainSignificance (VarID:630249), and to our current knowledge has not been reported in affected individuals in the literature. Given the lack of compelling evidence for its pathogenicity, the c.11303T>C p.(Ile3768Thr) variant identified in the APOB gene is reported as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV001856115 SCV002797744 uncertain significance Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 2021-10-16 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004535907 SCV004119033 uncertain significance APOB-related disorder 2023-04-07 criteria provided, single submitter clinical testing The APOB c.11303T>C variant is predicted to result in the amino acid substitution p.Ile3768Thr. This variant is also described using legacy nomenclature as p.Ile3741Thr, has been reported in an individual with hypertriglyceridemia (Johansen et al. 2010. PubMed ID: 20657596. Table S1). This variant has also been reported in a cohort study with lipid levels and coronary artery disease (Lu et al. 2017. PubMed ID: 29083407). This variant is reported in 0.050% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-21228437-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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