ClinVar Miner

Submissions for variant NM_001193466.2(KANSL1):c.3056G>A (p.Arg1019His) (rs781056926)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000543264 SCV000895108 uncertain significance Koolen-de Vries syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000187788 SCV000241385 uncertain significance not provided 2014-05-16 criteria provided, single submitter clinical testing This variant is denoted p.Arg1019His:c.3056 G>A in the KANSL1 gene (NM_001193466.1). The R1019H 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. This substitution occurs at a position that is conserved across mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the R1019H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, and missense mutations in nearby residues have not been reported. Therefore, based on the currently available information, it is unclear whether R1019H is a pathogenic mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Invitae RCV000543264 SCV000645058 uncertain significance Koolen-de Vries syndrome 2018-03-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1019 of the KANSL1 protein (p.Arg1019His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs781056926, 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: 205800). 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: "Probably 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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