Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002031728 | SCV002312498 | uncertain significance | DICER1-related tumor predisposition | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 126 of the DICER1 protein (p.Asn126Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DICER1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1524451). 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 not expected to disrupt DICER1 protein function. 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 | RCV003161311 | SCV003856112 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-24 | criteria provided, single submitter | clinical testing | The p.N126Y variant (also known as c.376A>T), located in coding exon 3 of the DICER1 gene, results from an A to T substitution at nucleotide position 376. The asparagine at codon 126 is replaced by tyrosine, an amino acid with 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. |
Fulgent Genetics, |
RCV005008444 | SCV005630499 | uncertain significance | Euthyroid goiter; Rhabdomyosarcoma, embryonal, 2; Pleuropulmonary blastoma; Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome | 2024-03-24 | criteria provided, single submitter | clinical testing |