ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.407G>A (p.Arg136His)

gnomAD frequency: 0.00002  dbSNP: rs775139340
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000557552 SCV000651309 uncertain significance Hereditary sensory neuropathy-deafness-dementia syndrome 2023-03-15 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with DNMT1-related conditions. 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 472274). This variant is present in population databases (rs775139340, gnomAD 0.04%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 136 of the DNMT1 protein (p.Arg136His).
Ambry Genetics RCV002324034 SCV002628883 likely benign Inborn genetic diseases 2020-02-20 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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