Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001021194 | SCV001182776 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-20 | criteria provided, single submitter | clinical testing | The p.Q1269E variant (also known as c.3805C>G), located in coding exon 20 of the DICER1 gene, results from a C to G substitution at nucleotide position 3805. The glutamine at codon 1269 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is poorly 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 | RCV001223924 | SCV001396094 | uncertain significance | DICER1-related tumor predisposition | 2023-11-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1269 of the DICER1 protein (p.Gln1269Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DICER1-related conditions. ClinVar contains an entry for this variant (Variation ID: 824240). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Sema4, |
RCV001021194 | SCV002532579 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-29 | criteria provided, single submitter | curation |