ClinVar Miner

Submissions for variant NM_001193466.2(KANSL1):c.868C>T (p.Arg290Ter) (rs149830411)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486096 SCV000570441 pathogenic not provided 2017-12-13 criteria provided, single submitter clinical testing The R290X variant in the KANSL1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R290X variant is observed in 16/277,204 alleles in large population cohorts, however, the reported allele frequency is likely from the inverted haplotype (Lek et al., 2016). We interpret R290X as a pathogenic variant.
Ambry Genetics RCV000623046 SCV000742976 likely pathogenic Inborn genetic diseases 2017-11-17 criteria provided, single submitter clinical testing
Geisinger Autism and Developmental Medicine Institute,Geisinger Health System RCV000678306 SCV000804365 pathogenic Koolen-de Vries syndrome 2018-03-19 criteria provided, single submitter provider interpretation This variant was identified in a 12 year old female with a history of intellectual disability, hypotonia, short stature, atrial septal defect, patent ductus arteriosus, multicystic dysplastic left kidney, congenital valgus foot deformity, constipation, and dysphagia. Dysmorphic facial features include coarse facies, hypertelorism, epicanthal folds, broad nasal tip, and wide spaced teeth. The variant is present in the gnomAD Finnish population at 0.058% but is absent from all other populations with sufficient data. The presence of an inversion polymorphism at 17q21.31 which overlaps KANSL1 complicates the interpretation of this variant. The proband is adopted and parental samples were not available. However, there was very strong clinical correlation between this patient's clinical features and Koolen-DeVries syndrome. In addition, whole exome sequencing identified an additional VUS in a gene of uncertain significance.

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