ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.410C>T (p.Thr137Met) (rs377146699)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000534735 SCV000410263 likely benign Hereditary sensory neuropathy type IE 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae RCV000534735 SCV000651310 uncertain significance Hereditary sensory neuropathy type IE 2019-12-24 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 137 of the DNMT1 protein (p.Thr137Met). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs377146699, ExAC 0.01%). This variant has not been reported in the literature in individuals with a DNMT1-related disease. ClinVar contains an entry for this variant (Variation ID: 327924). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; 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, this variant has uncertain impact on DNMT1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000734145 SCV000862264 uncertain significance not provided 2018-07-06 criteria provided, single submitter clinical testing

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