Submissions for variant NM_015443.4(KANSL1):c.1277G>A (p.Arg426His)

gnomAD frequency: 0.00006  dbSNP: rs764291274

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187774	SCV000241371	likely benign	not specified	2014-11-24	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000187774	SCV004029289	uncertain significance	not specified	2023-07-20	criteria provided, single submitter	clinical testing	Variant summary: KIAA1267 (KANSL1) c.1277G>A (p.Arg426His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.2e-05 in 277564 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1277G>A in individuals affected with Koolen-De Vries Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.