Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001020681 | SCV001182191 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-28 | criteria provided, single submitter | clinical testing | The p.N1200S variant (also known as c.3599A>G), located in coding exon 20 of the DICER1 gene, results from an A to G substitution at nucleotide position 3599. The asparagine at codon 1200 is replaced by serine, an amino acid with highly similar properties. This amino acid position is not well 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. |
| Labcorp Genetics |
RCV001873336 | SCV002216581 | uncertain significance | DICER1-related tumor predisposition | 2020-12-25 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 1200 of the DICER1 protein (p.Asn1200Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. 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. ClinVar contains an entry for this variant (Variation ID: 823969). 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. 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. |