ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.1886C>T (p.Thr629Met)

gnomAD frequency: 0.00001  dbSNP: rs750410087
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000528058 SCV000658156 uncertain significance DICER1-related tumor predisposition 2024-01-17 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 629 of the DICER1 protein (p.Thr629Met). This variant is present in population databases (rs750410087, 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: 477072). 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 RCV000565943 SCV000661933 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-06 criteria provided, single submitter clinical testing The p.T629M variant (also known as c.1886C>T), located in coding exon 10 of the DICER1 gene, results from a C to T substitution at nucleotide position 1886. The threonine at codon 629 is replaced by methionine, an amino acid with similar properties. 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.
Sema4, Sema4 RCV000565943 SCV002532480 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-29 criteria provided, single submitter curation
Baylor Genetics RCV003470771 SCV004193421 uncertain significance Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome 2023-07-29 criteria provided, single submitter clinical testing

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