ClinVar Miner

Submissions for variant NM_015443.4(KANSL1):c.1276C>T (p.Arg426Cys)

gnomAD frequency: 0.00005  dbSNP: rs757224600
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001705010 SCV000241370 likely benign not provided 2020-11-20 criteria provided, single submitter clinical testing
Invitae RCV001061422 SCV001226165 uncertain significance Koolen-de Vries syndrome 2021-09-01 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. Variants with ambiguous mapping are still reported relative to the KANSL1 transcript. This sequence change replaces arginine with cysteine at codon 426 of the KANSL1 protein (p.Arg426Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. 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. ClinVar contains an entry for this variant (Variation ID: 205785). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

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