Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001220382 | SCV001392368 | uncertain significance | Hereditary sensory neuropathy-deafness-dementia syndrome | 2022-08-06 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 949009). This variant has not been reported in the literature in individuals affected with DNMT1-related conditions. This variant is present in population databases (rs377146699, gnomAD 0.04%). This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 137 of the DNMT1 protein (p.Thr137Arg). |
| Ambry Genetics | RCV002322064 | SCV002632452 | likely benign | Inborn genetic diseases | 2021-10-14 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |