ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.737G>A (p.Arg246His)

gnomAD frequency: 0.00004  dbSNP: rs771381056
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000649358 SCV000771185 uncertain significance Hereditary sensory neuropathy-deafness-dementia syndrome 2024-01-15 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 246 of the DNMT1 protein (p.Arg246His). This variant is present in population databases (rs771381056, gnomAD 0.01%), and has an allele count higher than expected for a pathogenic variant. 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: 539601). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx RCV001584496 SCV001813662 likely benign not provided 2020-03-03 criteria provided, single submitter clinical testing

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