ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.3668G>A (p.Arg1223His) (rs757460628)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000813215 SCV000953561 uncertain significance Hereditary sensory neuropathy type IE 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1223 of the DNMT1 protein (p.Arg1223His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs757460628, ExAC 0.02%). This variant has not been reported in the literature in individuals with DNMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 438391). 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.
Genetics and Molecular Pathology Laboratory,Hudson Institute of Medical Research RCV000625706 SCV000599436 uncertain significance Beckwith-Wiedemann syndrome no assertion criteria provided research This variant was identified in heterozygous form in 1 of 53 cases with Beckwith Wiedemann syndrome with loss of KCNQ1OT1 at Imprinting centre 2 on 11p15.5. The variant frequency in dbSNP is 0.00002.

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