Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001138485 | SCV001298542 | uncertain significance | Familial hypobetalipoproteinemia 1 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV001138486 | SCV001298543 | uncertain significance | Hypercholesterolemia, autosomal dominant, type B | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Ambry Genetics | RCV002431731 | SCV002740735 | uncertain significance | Cardiovascular phenotype | 2023-08-25 | criteria provided, single submitter | clinical testing | The p.A871T variant (also known as c.2611G>A), located in coding exon 18 of the APOB gene, results from a G to A substitution at nucleotide position 2611. The alanine at codon 871 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and threonine is the reference amino acid in other 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, |
RCV002491155 | SCV002781955 | uncertain significance | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2021-07-19 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002491155 | SCV003289370 | likely benign | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2023-12-29 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001356201 | SCV001551305 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The APOB p.Ala871Thr variant was not identified in the literature nor was it identified in Cosmic. The variant was identified in dbSNP (ID: rs144622446), ClinVar (classified as a VUS by Color; associated condition is Familial hypercholesterolemia). The variant was also found in control databases in 32 of 282392 chromosomes at a frequency of 0.000113 (Genome Aggregation Database Feb 27, 2017) and was observed in the following populations: European (non-Finnish) in 27 of 128764 chromosomes (freq: 0.00021), African in 4 of 24948 chromosomes (freq: 0.00016) and Other in 1 of 7216 chromosomes (freq: 0.000139), while the variant was not observed in the Latino, Ashkenazi Jewish, East Asian, European (Finnish) and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Ala871 residue is not conserved in mammals or other organisms, and none of the computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |