ClinVar Miner

Submissions for variant NM_001193466.2(KANSL1):c.3053C>T (p.Thr1018Ile) (rs145863194)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000442828 SCV000535518 likely benign not specified 2018-02-22 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000697747 SCV000826374 uncertain significance Koolen-de Vries syndrome 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 1018 of the KANSL1 protein (p.Thr1018Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs145863194, ExAC 0.05%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with KANSL1-related disease. ClinVar contains an entry for this variant (Variation ID: 392273). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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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