ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.734C>T (p.Thr245Met) (rs143598088)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000597356 SCV000703590 uncertain significance not provided 2016-12-13 criteria provided, single submitter clinical testing
Invitae RCV000797299 SCV000936848 uncertain significance Hereditary sensory neuropathy type IE 2018-07-31 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 245 of the DNMT1 protein (p.Thr245Met). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs143598088, ExAC 0.03%). This variant has not been reported in the literature in individuals with DNMT1-related disease. ClinVar contains an entry for this variant (Variation ID: 498534). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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