Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004567446 | SCV000647482 | uncertain significance | Familial adenomatous polyposis 1 | 2023-11-17 | 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 1313 of the APC protein (p.Thr1313Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with familial adenomatous polyposis (PMID: 23159591). ClinVar contains an entry for this variant (Variation ID: 217974). 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, |
RCV001180271 | SCV001345153 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-07-19 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 1313 of the APC protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in an individual affected with familial adenomatous polyposis (PMID: 23159591). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). 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. |
| Ambry Genetics | RCV001180271 | SCV004069592 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-08 | criteria provided, single submitter | clinical testing | The p.T1313A variant (also known as c.3937A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 3937. The threonine at codon 1313 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well 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. |
| Mayo Clinic Laboratories, |
RCV000202157 | SCV000256982 | uncertain significance | not specified | no assertion criteria provided | research |