Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000522656 | SCV000620108 | likely pathogenic | not provided | 2017-08-17 | criteria provided, single submitter | clinical testing | The c.1196 A>G variant in the KDM1A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.1196 A>G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In-silico splice prediction models predict that c.1196 A>G may create a cryptic splice donor site upstream of the natural splice donor site in intron 11, which may supplant the natural donor site. However, in the absence of RNA/functional studies, the actual effect of the c.1196 A>G change in this individual is unknown. If c.1196 A>G does not alter splicing, it will result in the D399G missense change. The D399G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret c.1196 A>G as a likely pathogenic variant. |
| Génétique des Maladies du Développement, |
RCV001527312 | SCV001737949 | likely pathogenic | Intellectual disability | 2021-06-22 | criteria provided, single submitter | clinical testing | absent from gnomAD, de novo, predicted deleterious, already in ClinVar. Limited phenotype evidence |