ClinVar Miner

Submissions for variant NM_015443.4(KANSL1):c.1295G>A (p.Arg432His) (rs754111757)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001295298 SCV001484213 uncertain significance Koolen-de Vries syndrome 2020-07-08 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 arginine with histidine at codon 432 of the KANSL1 protein (p.Arg432His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C2. The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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. 5

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