Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000798910 | SCV000938553 | uncertain significance | Perlman syndrome | 2020-08-21 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with lysine at codon 362 of the DIS3L2 protein (p.Thr362Lys). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and lysine. This variant is present in population databases (rs762225594, ExAC 0.002%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DIS3L2-related conditions. |