ClinVar Miner

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

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Total submissions: 2
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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 2019-12-11 criteria provided, single submitter clinical testing 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. This variant is present in population databases (rs200903841, ExAC 0.03%). This variant has not been reported in the literature in individuals with KANSL1-related disease. 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. 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.

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