Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV003228666 | SCV003925384 | uncertain significance | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2022-04-01 | criteria provided, single submitter | clinical testing | The c.5898C>A p.(His1966Gln) missense variant identified 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.5898C>A variant is located in exon 26 of this 29-exon gene, and predicted to replace a moderately conserved histidine amino acid with glutamine at position 1966. In silico predictions are inconclusive of deleterious effect (CADD v1.6= 24.2 REVEL=0.182); however, there are no functional studies to support or refute these predictions. Based on available evidence the c.5898C>A p.(His1966Gln) variant identified in APOB is classified as a Variant of Uncertain Significance. |