ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.1983G>T (p.Glu661Asp)

gnomAD frequency: 0.00001  dbSNP: rs781764761
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000694070 SCV000822497 uncertain significance Hereditary sensory neuropathy-deafness-dementia syndrome 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 661 of the DNMT1 protein (p.Glu661Asp). This variant is present in population databases (rs781764761, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with DNMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 572640). 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 DNMT1 protein function with a negative 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.

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