Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV003228591 | SCV003925161 | uncertain significance | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2022-06-08 | criteria provided, single submitter | clinical testing | The c.13029T>A (p.Tyr4343Ter) variant in the APOB gene has not previously been reported in the literature or public variant repositories (ClinVar and LOVD), and is absent from population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases. The c.13029T>A (p.Tyr4343Ter) stop-gain variant in APOB is located in exon 29 of this 29-exon gene, predicted to escape nonsense mediated decay and result in loss of the last 221 amino acid. Loss-of-function variants that are downstream to the c.13029T>A variant have been reported in the literature in a few individuals with hypobetalipoproteinemia, hypercholesterolemia or hypertriglyceridemia [PMID: 26020417, 33207932,20657596, others]; and in ClinVar [ClinVar ID: 923102, 928004, 440513, others] in individuals with APOB-Related Disorders without providing unequivocal conclusions about an association between these variants and APOB-Related Disorders. To our knowledge, functional assays have not been performed for these variants. Based on available evidence this c.13029T>A p.Tyr4343Ter variant identified in APOB is classified as a Variant of Uncertain Significance. |