Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000563046 | SCV000667631 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-05 | criteria provided, single submitter | clinical testing | The p.T938A variant (also known as c.2812A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 2812. The threonine at codon 938 is replaced by alanine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587407 | SCV000694018 | uncertain significance | not provided | 2016-07-15 | criteria provided, single submitter | clinical testing | Variant summary: The c.2812A>G (p.Thr938Ala) in APC gene is a missense change that involves a non-conserved nucleotide and 4/5 in silico tools predict benign outcome. The variant of interest is located outside of any known functional domain. The variant is absent from the control population dataset of ExAC and has not, to our knowledge, been reported in affected individuals via published reports or by reputable databases/clinical laboratories. Taking together, the variant was classified as VUS. |
| Labcorp Genetics |
RCV002528066 | SCV000768269 | uncertain significance | Familial adenomatous polyposis 1 | 2023-12-27 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 938 of the APC protein (p.Thr938Ala). 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: 482398). 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 | RCV002248783 | SCV002516926 | uncertain significance | not specified | 2023-06-19 | criteria provided, single submitter | clinical testing |