Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001319467 | SCV001510210 | uncertain significance | Koolen-de Vries syndrome | 2022-08-15 | 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. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 1019960). This variant has not been reported in the literature in individuals with KANSL1-related conditions. The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 359 of the KANSL1 protein (p.Ser359Gly). |
| New York Genome Center | RCV001319467 | SCV002548908 | uncertain significance | Koolen-de Vries syndrome | 2021-08-27 | criteria provided, single submitter | clinical testing |