Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001026546 | SCV001188948 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-22 | criteria provided, single submitter | clinical testing | The p.I2515R variant (also known as c.7544T>G), located in coding exon 15 of the APC gene, results from a T to G substitution at nucleotide position 7544. The isoleucine at codon 2515 is replaced by arginine, 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. |
| Labcorp Genetics |
RCV004570070 | SCV002199158 | uncertain significance | Familial adenomatous polyposis 1 | 2024-10-06 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2515 of the APC protein (p.Ile2515Arg). 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: 827111). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
| Gene |
RCV004768793 | SCV005377155 | uncertain significance | not provided | 2023-11-12 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Not observed in any biliary tract cancer cases, but was observed in unaffected/cancer-free controls (PMID: 36243179); This variant is associated with the following publications: (PMID: 36243179) |