Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003742703 | SCV000647501 | uncertain significance | Familial adenomatous polyposis 1 | 2022-06-13 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 469953). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1401 of the APC protein (p.Ile1401Val). |
| Ambry Genetics | RCV001022043 | SCV001183732 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-04 | criteria provided, single submitter | clinical testing | The p.I1401V variant (also known as c.4201A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 4201. The isoleucine at codon 1401 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Illumina Laboratory Services, |
RCV001155475 | SCV001316903 | uncertain significance | APC-Associated Polyposis Disorders | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Baylor Genetics | RCV002528514 | SCV004198979 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-10 | criteria provided, single submitter | clinical testing |