Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Robarts Research Institute, |
RCV000660678 | SCV000782836 | likely benign | Hypercholesterolemia, familial, 1 | 2018-01-02 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002442382 | SCV002753571 | uncertain significance | Cardiovascular phenotype | 2023-07-26 | criteria provided, single submitter | clinical testing | The p.A1018T variant (also known as c.3052G>A), located in coding exon 20 of the APOB gene, results from a G to A substitution at nucleotide position 3052. The alanine at codon 1018 is replaced by threonine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs149357946. Based on data from ExAC, the A allele has an overall frequency of less than 0.01% (2/106206). Based on data from the 1000 Genomes Project, the A allele has an overall frequency of approximately 0.05% (1/2098) total alleles studied. The highest observed frequency was 0.56% (1/178) Japanese alleles. This amino acid position is not well 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 variant remains unclear. |
New York Genome Center | RCV003227821 | SCV003925337 | uncertain significance | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2022-04-08 | criteria provided, single submitter | clinical testing | The c.3052G>A (p.Ala1018Thr) missense variant identified in the APOB gene has not been reported in affected individuals in the literature. The variant has four heterozygous in the gnomAD(v3) and eleven heterozygous in TOPMed Freeze 8 database suggesting it is not a common benign variant in the populations represented in that database. The variant affects a moderately conserved residue and multiple in silico prediction tools provide conflicting predictions about the potential pathogenicity of this variant (CADD=22.1, REVEL score = 0.180). Based on the available evidence, the c.3052G>A (p.Ala1018Thr) variant identified in the APOB gene is reported as a Variant of Uncertain Significance. |
Labcorp Genetics |
RCV003227821 | SCV004610353 | likely benign | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2024-10-31 | criteria provided, single submitter | clinical testing |