Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000165015 | SCV000215710 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-22 | criteria provided, single submitter | clinical testing | The p.D432G variant (also known as c.1295A>G), located in coding exon 9 of the APC gene, results from an A to G substitution at nucleotide position 1295. The aspartic acid at codon 432 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV003765025 | SCV000552630 | uncertain significance | Familial adenomatous polyposis 1 | 2023-11-29 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 432 of the APC protein (p.Asp432Gly). This variant is not present in population databases (gnomAD no frequency). 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: 185572). 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. |
Color Diagnostics, |
RCV000165015 | SCV001358308 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-18 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glycine at codon 432 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has not been identified 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. |
Preventiongenetics, |
RCV003398838 | SCV004103873 | uncertain significance | APC-related condition | 2023-09-27 | criteria provided, single submitter | clinical testing | The APC c.1295A>G variant is predicted to result in the amino acid substitution p.Asp432Gly. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/185572/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |