Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000644674 | SCV000766377 | uncertain significance | Koolen-de Vries syndrome | 2019-06-19 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 966 of the KANSL1 protein (p.Thr966Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs763252158, ExAC 0.003%). This variant has not been reported in the literature in individuals with KANSL1-related disease. 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: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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. |