Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Pittsburgh Clinical Genomics Laboratory, |
RCV004785130 | SCV005397631 | uncertain significance | Kleefstra syndrome 2 | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence variant is a single nucleotide substitution (G>C) at position 28 of the coding sequence of the KMT2C gene that results in a glutamic acid to glutamine amino acid change at residue 10 of the lysine methyltransferase 2C protein. This variant is absent from ClinVar and the gnomAD v4 population database (0 of approximately 600,000 alleles). To our knowledge, this variant has not been observed in an individual affected by a KMT2C-related disorder in the published literature. Multiple bioinformatic tools provide conflicting predictions concerning this Glu to Gln amino acid change, and the Glu10 residue at this position is highly conserved across the vertebrate species examined. Studies examining the functional consequence of this variant have not been published, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this a variant of uncertain significance. ACMG Criteria: BP1, PM2 |