Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001223806 | SCV001395972 | uncertain significance | DICER1-related tumor predisposition | 2020-03-18 | 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. 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 has not been reported in the literature in individuals with DICER1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with arginine at codon 1612 of the DICER1 protein (p.Ser1612Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. |
Ambry Genetics | RCV002339595 | SCV002638043 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-23 | criteria provided, single submitter | clinical testing | The p.S1612R variant (also known as c.4836C>A), located in coding exon 22 of the DICER1 gene, results from a C to A substitution at nucleotide position 4836. The serine at codon 1612 is replaced by arginine, an amino acid with dissimilar properties. This alteration was identified in 1/1358 non-cancer control individuals and in 0/57 cases, in a study looking at cancer predisposition mutations in patients with cutaneous melanoma and a history of at least two additional non-cutaneous melanoma primary cancers. (Pritchard AL et al. PLoS ONE, 2018 Apr;13:e0194098). 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. |