Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000270228 | SCV000330164 | pathogenic | not provided | 2016-01-08 | criteria provided, single submitter | clinical testing | The c.16469_16472delAAGA pathogenic variant in the KMT2D gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant causes a frameshift starting with codon Lysine 5490, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 18 of the new reading frame, denoted p.Lys5490ArfgsX18. This variant is predicted to cause protein truncation in the SET domain, as the last 48 amino acid residues of the protein are replaced with 17 incorrect amino acids. Other protein truncating pathogenic variants have been described in associated with Kabuki syndrome (Ng et al. 2010, Hannibal et al. 2011). This variant was not observed in approximately 6200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.16469_16472delAAGA as a pathogenic variant. |