ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.1757G>C (p.Ser586Thr)

gnomAD frequency: 0.00001  dbSNP: rs1201469324
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001349527 SCV001543878 uncertain significance Hereditary sensory neuropathy-deafness-dementia syndrome 2020-07-22 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 586 of the DNMT1 protein (p.Ser586Thr). The serine residue is moderately conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DNMT1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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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