Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000159556 | SCV000209527 | uncertain significance | not provided | 2019-08-26 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Illumina Laboratory Services, |
RCV000291608 | SCV000452014 | uncertain significance | APC-Associated Polyposis Disorders | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000563203 | SCV000667548 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-16 | criteria provided, single submitter | clinical testing | The p.D1532N variant (also known as c.4594G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 4594. The aspartic acid at codon 1532 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is 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 alteration remains unclear. |
Invitae | RCV003534409 | SCV000950867 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-26 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1532 of the APC protein (p.Asp1532Asn). This variant is present in population databases (rs730881251, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 181807). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Mendelics | RCV000810645 | SCV001136916 | uncertain significance | Familial adenomatous polyposis 1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000563203 | SCV001347426 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-11 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with asparagine at codon 1532 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with ovarian cancer (DOI: 10.1101/2021.04.15.21255554). This variant has been identified in 2/250372 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000159556 | SCV001469306 | uncertain significance | not provided | 2019-10-16 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002509260 | SCV002819422 | uncertain significance | not specified | 2022-12-11 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000810645 | SCV004198758 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-15 | criteria provided, single submitter | clinical testing |