Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003742600 | SCV000647224 | uncertain significance | Familial adenomatous polyposis 1 | 2022-07-06 | 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 469736). 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 asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 741 of the APC protein (p.Asn741Asp). |
Ambry Genetics | RCV003159864 | SCV003866351 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-23 | criteria provided, single submitter | clinical testing | The p.N741D variant (also known as c.2221A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 2221. The asparagine at codon 741 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is conserved. 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. |
Prevention |
RCV003900199 | SCV004716214 | uncertain significance | APC-related condition | 2023-11-06 | criteria provided, single submitter | clinical testing | The APC c.2221A>G variant is predicted to result in the amino acid substitution p.Asn741Asp. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/485596/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |