Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000822600 | SCV000963410 | uncertain significance | Koolen-de Vries syndrome | 2021-09-17 | 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. Variants with ambiguous mapping are still reported relative to the KANSL1 transcript. This sequence change replaces lysine with glutamic acid at codon 93 of the KANSL1 protein (p.Lys93Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with KANSL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 664497). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |