Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001010725 | SCV001170962 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-27 | criteria provided, single submitter | clinical testing | The p.K427R variant (also known as c.1280A>G), located in coding exon 7 of the DICER1 gene, results from an A to G substitution at nucleotide position 1280. The lysine at codon 427 is replaced by arginine, 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. |
| Invitae | RCV001235469 | SCV001408155 | uncertain significance | DICER1-related tumor predisposition | 2021-07-26 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with DICER1-related conditions. 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"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with arginine at codon 427 of the DICER1 protein (p.Lys427Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. |