ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.3566A>G (p.Tyr1189Cys)

dbSNP: rs1891140921
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001042721 SCV001206421 uncertain significance DICER1-related tumor predisposition 2019-11-25 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 1189 of the DICER1 protein (p.Tyr1189Cys). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant has not been reported in the literature in individuals with DICER1-related disease. 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain.
Ambry Genetics RCV002454300 SCV002615584 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-10 criteria provided, single submitter clinical testing The p.Y1189C variant (also known as c.3566A>G), located in coding exon 20 of the DICER1 gene, results from an A to G substitution at nucleotide position 3566. The tyrosine at codon 1189 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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.

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