Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000792206 | SCV000931486 | uncertain significance | Hereditary sensory neuropathy-deafness-dementia syndrome | 2018-09-03 | 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with DNMT1-related disease. This variant is present in population databases (rs777416084, ExAC 0.009%). This sequence change replaces glycine with cysteine at codon 946 of the DNMT1 protein (p.Gly946Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. |