Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Johns Hopkins Genomics, |
RCV001200881 | SCV001371786 | uncertain significance | Kleefstra syndrome 2 | 2020-01-06 | criteria provided, single submitter | clinical testing | This KMT2C variant is absent from a large population dataset, and has not been reported in the literature to our knowledge. A different, stopgain variant at the same position (p.Arg1292Ter) has been previously reported as a VUS. Three bioinformatic tools queried predict that p.Arg1292Gly would be possibly damaging, and the arginine residue at this position is evolutionarily conserved across the vertebrates assessed. Additionally, bioinformatic analysis predicts that this variant would not affect normal exon 25 splicing, although this has not been confirmed experimentally to our knowledge. This substitution does not occur in any known functional domain of the KMT2C protein. Due to insufficient evidence, we consider the clinical significance of c.3874C>G to be uncertain at this time. |