Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003538618 | SCV001391851 | uncertain significance | Familial adenomatous polyposis 1 | 2019-04-10 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with APC-related disease. This sequence change replaces asparagine with tyrosine at codon 1548 of the APC protein (p.Asn1548Tyr). The asparagine residue is moderately conserved and there is a large physicochemical difference between asparagine and tyrosine. |
Ambry Genetics | RCV002327517 | SCV002633615 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-28 | criteria provided, single submitter | clinical testing | The p.N1548Y variant (also known as c.4642A>T), located in coding exon 15 of the APC gene, results from an A to T substitution at nucleotide position 4642. The asparagine at codon 1548 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is not well 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. |