Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001042559 | SCV001206245 | uncertain significance | Hoyeraal-Hreidarsson syndrome; Autosomal recessive dyskeratosis congenita | 2019-04-19 | 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 DCLRE1B-related conditions. This variant is present in population databases (rs745991382, ExAC 0.001%). This sequence change replaces threonine with methionine at codon 251 of the DCLRE1B protein (p.Thr251Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. |