ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.4991C>T (p.Ser1664Leu)

gnomAD frequency: 0.00001  dbSNP: rs988095775
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000466310 SCV000553553 uncertain significance DICER1-related tumor predisposition 2024-10-29 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1664 of the DICER1 protein (p.Ser1664Leu). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 412095). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DICER1 protein function with a negative predictive value of 95%. 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 RCV000563940 SCV000661990 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-06 criteria provided, single submitter clinical testing The p.S1664L variant (also known as c.4991C>T), located in coding exon 22 of the DICER1 gene, results from a C to T substitution at nucleotide position 4991. The serine at codon 1664 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV004568095 SCV005059470 uncertain significance Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome 2024-02-24 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005010369 SCV005637731 uncertain significance Euthyroid goiter; Rhabdomyosarcoma, embryonal, 2; Pleuropulmonary blastoma; Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome 2024-02-16 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.