Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001838362 | SCV001227528 | likely benign | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2024-04-12 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002339308 | SCV002643931 | uncertain significance | Cardiovascular phenotype | 2024-03-21 | criteria provided, single submitter | clinical testing | The p.I1652L variant (also known as c.4954A>C), located in coding exon 26 of the APOB gene, results from an A to C substitution at nucleotide position 4954. The isoleucine at codon 1652 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |
| New York Genome Center | RCV001838362 | SCV004046635 | uncertain significance | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2022-12-19 | criteria provided, single submitter | clinical testing | The c.4954A>C p.(Ile1652Leu) missense variant identified in the APOB gene has previously been deposited in ClinVar as a variant of uncertain significance (2) and likely benign (1) [Variation ID: 857100] and to our current knowledge has not been reported in an affected individual in the literature. The c.4954A>C variant is observed in 10 alleles (~0. 0.002% minor allele frequency with 0 homozygotes) in population databases (gnomAD v2.1.1 and v3.1.2, TOPMedFreeze 8), suggesting it is not a common benign variant in the populations represented in those databases. The c.4954A>C variant is located in exon 26 of this 29-exon gene, and predicted to replace a weakly conserved isoleucine amino acid with leucine at position 1652 of the encoded protein. In silico algorithms do not predict a damaging effect to the function of the canonical protein (REVEL=0.038); however, there are no functional studies to support or refute these predictions. Based on available evidence the c.4954A>C p.(Ile1652Leu) variant identified in APOB is classified as a Variant of UncertainSignificance. |
| Mayo Clinic Laboratories, |
RCV004792703 | SCV005411632 | uncertain significance | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | BP4 |