Submissions for variant NM_015443.4(KANSL1):c.1186C>T (p.Gln396Ter) (rs796052603)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187802	SCV000241399	likely pathogenic	not provided	2015-01-14	criteria provided, single submitter	clinical testing	This variant is denoted p.Gln396Ter (CAG>TAG): c.1186 C>T in exon 2 of the KANSL1 gene (NM_001193466.1). The Q396X variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Nonsense mutations in the KANSL1 gene have been reported in association with Koolen-DeVries syndrome. The Q396X variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in EPILEPSYV2-1 panel(s).
Invitae	RCV001317571	SCV001508240	uncertain significance	Koolen-de Vries syndrome	2020-05-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln396*) in the KANSL1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with epilepsy and/or neurodevelopmental disorders (PMID: 29655203). ClinVar contains an entry for this variant (Variation ID: 205814). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.