ClinVar Miner

Submissions for variant NM_001193466.2(KANSL1):c.805C>T (p.Pro269Ser) (rs200903841)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187801 SCV000241398 uncertain significance not provided 2014-03-25 criteria provided, single submitter clinical testing This variant is denoted p.Pro269Ser (P269S) CCC>TCC: c.805 C>T in exon 2 of the KANSL1 gene (NM_001193466.1).The P269S variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P269S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. To date, missense mutations have not been associated with 17q21.31 microdeletion syndrome. Therefore, based on the currently available information, it is still unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Invitae RCV000644667 SCV000766370 uncertain significance Koolen-de Vries syndrome 2020-09-01 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 proline with serine at codon 269 of the KANSL1 protein (p.Pro269Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. 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. ClinVar contains an entry for this variant (Variation ID: 205813). 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. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.