Total submissions: 2
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. |