Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001837774 | SCV000284765 | likely benign | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2023-12-08 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002450670 | SCV002739873 | uncertain significance | Cardiovascular phenotype | 2023-02-02 | criteria provided, single submitter | clinical testing | The p.N886S variant (also known as c.2657A>G), located in coding exon 18 of the APOB gene, results from an A to G substitution at nucleotide position 2657. The asparagine at codon 886 is replaced by serine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV001837774 | SCV002775815 | uncertain significance | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2021-10-25 | criteria provided, single submitter | clinical testing | |
New York Genome Center | RCV001837774 | SCV003925180 | uncertain significance | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2022-06-15 | criteria provided, single submitter | clinical testing | The c.2657A>G p.(Asn886Ser) variant identified in the APOB gene is predicted to result in the substitution of an Asparagine for Serineat amino acid 886/4564 (exon 18/29). This variant is found with low frequency in population databases gnomAD, BRAVO-TOPMed Freeze 8, All of Us (allele frequency=1.1e-4) suggesting it is not a common benign variant in the populations represented in those databases. In silico algorithms do not predict a damaging effect to the function of the canonical protein (REVEL=0.153). This variant reported in ClinVar as a Variant of Uncertain Significance [VarID:237742] 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.2657A>Gp.(Asn886Ser) variant identified in the APOB gene is reported as a Variant of Uncertain Significance. |