Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001062036 | SCV001226805 | uncertain significance | DICER1-related tumor predisposition | 2023-12-08 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1578 of the DICER1 protein (p.Ala1578Thr). This variant is present in population databases (rs760830088, gnomAD 0.002%). This missense change has been observed in individual(s) with bladder and uterine cancer (PMID: 30672147). ClinVar contains an entry for this variant (Variation ID: 856552). 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 expected to disrupt DICER1 protein function with a positive predictive value of 80%. 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. |
Ambry Genetics | RCV002339304 | SCV002639112 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-07-07 | criteria provided, single submitter | clinical testing | The p.A1578T variant (also known as c.4732G>A), located in coding exon 22 of the DICER1 gene, results from a G to A substitution at nucleotide position 4732. The alanine at codon 1578 is replaced by threonine, an amino acid with similar properties. One study identified this variant in the germline of a 69-year-old Caucasian female with a history of uterine corpus endometrial carcinoma and a 70-year-old Caucasian male with a history of bladder urothelial carcinoma (Kim J et al. Mol Genet Genomic Med, 2019 03;7:e555). 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. |
Baylor Genetics | RCV003462592 | SCV004193365 | uncertain significance | Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome | 2023-09-22 | criteria provided, single submitter | clinical testing |