Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001316170 | SCV001506775 | uncertain significance | Koolen-de Vries syndrome | 2020-09-21 | criteria provided, single submitter | clinical testing | Due to the possible presence of a polymorphic segmental duplication, the location of the variant could not be unambiguously resolved. If the variant occurs in the KANSL1 gene, this sequence change replaces histidine with leucine at codon 427 of the KANSL1 or 17q21.31 segmental duplication protein (p.His427Leu). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and leucine. The frequency data for this variant in the population databases (ExAC) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This variant has not been reported in the literature in individuals with KANSL1-related conditions. 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: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C1). Until the location of this sequence change can be resolved, the clinical significance of this variant remains uncertain. It has been classified as a Variant of Uncertain Significance. 5 |