Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001231914 | SCV001404452 | uncertain significance | DICER1-related tumor predisposition | 2019-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with histidine at codon 467 of the DICER1 protein (p.Gln467His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DICER1-related conditions. 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"). 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. |
| Ambry Genetics | RCV002393576 | SCV002697740 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-28 | criteria provided, single submitter | clinical testing | The p.Q467H variant (also known as c.1401A>C), located in coding exon 8 of the DICER1 gene, results from an A to C substitution at nucleotide position 1401. The glutamine at codon 467 is replaced by histidine, 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. |