Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000704744 | SCV000833705 | uncertain significance | Hoyeraal-Hreidarsson syndrome; Autosomal recessive dyskeratosis congenita | 2018-04-12 | 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This sequence change replaces arginine with tryptophan at codon 46 of the DCLRE1B protein (p.Arg46Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs774397708, ExAC 0.001%). This variant has not been reported in the literature in individuals with DCLRE1B-related disease. |