Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001207613 | SCV001378975 | uncertain significance | DICER1-related tumor predisposition | 2021-06-19 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with serine at codon 66 of the DICER1 protein (p.Thr66Ser). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and serine. |
| Ambry Genetics | RCV002418697 | SCV002722901 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-05 | criteria provided, single submitter | clinical testing | The p.T66S variant (also known as c.197C>G), located in coding exon 2 of the DICER1 gene, results from a C to G substitution at nucleotide position 197. The threonine at codon 66 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. 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. |
| Gene |
RCV003317448 | SCV004021537 | uncertain significance | not provided | 2023-01-24 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |