Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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 | 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. 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). This variant is not present in population databases (ExAC no frequency). 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. |