ClinVar Miner

Submissions for variant NM_001193466.2(KANSL1):c.1270G>A (p.Glu424Lys) (rs780942888)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000424488 SCV000522973 likely benign not specified 2015-12-31 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 RCV001201462 SCV001372531 uncertain significance Koolen-de Vries syndrome 2020-10-01 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. If the variant occurs in the KANSL1 gene, this sequence change replaces glutamic acid with lysine at codon 424 of the KANSL1 protein (p.Glu424Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. 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: 382840). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C1). 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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