Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000236975 | SCV000293109 | uncertain significance | not provided | 2019-09-11 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect |
Invitae | RCV001857804 | SCV002125446 | uncertain significance | Hereditary sensory neuropathy-deafness-dementia syndrome | 2023-01-08 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DNMT1 protein function. ClinVar contains an entry for this variant (Variation ID: 245911). This variant has not been reported in the literature in individuals affected with DNMT1-related conditions. This variant is present in population databases (rs766051225, gnomAD 0.04%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1334 of the DNMT1 protein (p.Ala1334Val). |
Fulgent Genetics, |
RCV002479942 | SCV002793343 | uncertain significance | Autosomal dominant cerebellar ataxia, deafness and narcolepsy; Hereditary sensory neuropathy-deafness-dementia syndrome | 2021-11-24 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003165660 | SCV003887537 | likely benign | Inborn genetic diseases | 2023-01-09 | 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. |