Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV001839231 | SCV002099194 | uncertain significance | Kabuki syndrome 1 | 2021-03-26 | criteria provided, single submitter | clinical testing | The inherited c.7484C>T (p.Pro2495Leu) variant identified in the KMT2D gene substitutes a conserved Proline for Leucine at amino acid 2495/5538 (exon 32/55). This variant is absent from gnomAD(v3.1.1) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict the variant to be Damaging (SIFT; score: 0.03) and Benign (REVEL; score:0.472) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The p.Pro2495 residue is not within a mapped domain of KMT2D, but is in a region rich in Proline residues (UniProtKB:O14686). Given the lack of compelling evidence for its pathogenicity, the inherited c.7484C>T (p.Pro2495Leu) variant identified in the KMT2D gene is reported as a Variant of Uncertain Significance. |