Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001218556 | SCV001390444 | uncertain significance | DICER1-related tumor predisposition | 2023-06-25 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DICER1 protein function. ClinVar contains an entry for this variant (Variation ID: 947471). This variant has not been reported in the literature in individuals affected with DICER1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 1122 of the DICER1 protein (p.Cys1122Tyr). |
| Ambry Genetics | RCV002451494 | SCV002615481 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-16 | criteria provided, single submitter | clinical testing | The p.C1122Y variant (also known as c.3365G>A), located in coding exon 20 of the DICER1 gene, results from a G to A substitution at nucleotide position 3365. The cysteine at codon 1122 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |