ClinVar Miner

Submissions for variant NM_015443.4(KANSL1):c.1774C>T (p.Arg592Trp) (rs774841964)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000552242 SCV000645039 uncertain significance Koolen-de Vries syndrome 2017-05-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 592 of the KANSL1 protein (p.Arg592Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been shown to arise de novo in individuals affected with a seizure disorder (Invitae). However, previously reported disease-causing de novo variants in KANSL1 have been truncations or gene deletions (PMID: 2544363, 26424144, 22544367, 26306646). 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant has been observed to arise de novo in a single individual. In the absence of additional clinical or functional data, it has been classified as a Variant of Uncertain Significance.
Laboratoire Génétique Moléculaire, CHRU TOURS RCV001542080 SCV001760746 likely pathogenic not provided 2020-04-06 criteria provided, single submitter clinical testing

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