Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003534649 | SCV000824846 | uncertain significance | Familial adenomatous polyposis 1 | 2023-08-08 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 597 of the APC protein (p.Ala597Val). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 574374). 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. 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. |
| Ambry Genetics | RCV001013183 | SCV001173733 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-12 | criteria provided, single submitter | clinical testing | The p.A597V variant (also known as c.1790C>T), located in coding exon 14 of the APC gene, results from a C to T substitution at nucleotide position 1790. The alanine at codon 597 is replaced by valine, an amino acid with similar properties. This variant as detected in a cohort of 403 individuals that fulfilled the NCCN testing criteria for HBOC (Oliver J et al. Front Oncol, 2019 Dec;9:1429). 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. |