ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.925G>A (p.Ala309Thr)

gnomAD frequency: 0.00026  dbSNP: rs141888564
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001838018 SCV000777014 likely benign Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 2025-02-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284270 SCV001469954 uncertain significance not provided 2024-09-02 criteria provided, single submitter clinical testing The APOB c.925G>A (p.Ala309Thr) variant has not been reported in individuals with APOB-related conditions in the published literature. The frequency of this variant in the general population, 0.00073 (19/26134 chromosomes in Swedish subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
CeGaT Center for Human Genetics Tuebingen RCV001284270 SCV001746593 uncertain significance not provided 2021-04-01 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001816652 SCV002067940 uncertain significance not specified 2021-02-18 criteria provided, single submitter clinical testing DNA sequence analysis of the APOB gene demonstrated a sequence change, c.925G>A, in exon 9 that results in an amino acid change, p.Ala309Thr. This sequence change has been described in gnomAD with a low population frequency of 0.022% (dbSNP rs141888564). The p.Ala309Thr change affects a moderately conserved amino acid residue located in a domain of the APOB protein that is known to be functional. The p.Ala309Thr substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change does not appear to have been previously described in patients with APOB-related disorders. Due to the lack of sufficient evidences, the clinical significance of the p.Ala309Thr change remains unknown at this time.
Ambry Genetics RCV002369768 SCV002686498 benign Cardiovascular phenotype 2024-10-02 criteria provided, single submitter clinical testing This alteration is classified as 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.
Fulgent Genetics, Fulgent Genetics RCV001838018 SCV005655812 uncertain significance Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 2024-03-06 criteria provided, single submitter clinical testing

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