Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Pittsburgh Clinical Genomics Laboratory, |
RCV004784928 | SCV005397191 | uncertain significance | Kleefstra syndrome 2 | 2022-12-23 | criteria provided, single submitter | clinical testing | This sequence variant is a single nucleotide substitution (C>A) at coding position 13331 of the KMT2C gene that results in an alanine to aspartic acid amino acid change at residue 4444 of the KMT2C protein. This variant has not been previously reported in databases of clinically relevant variants (ClinVar) and has not been observed in individuals with KMT2C-related illness, to our knowledge. This variant is present in the gnomAD population database (1 of 250922 alleles or 0.0004%). Multiple bioinformatic tools predict that this variant would be damaging, and the Ala4444 residue is highly conserved across the vertebrate species examined. Functiol studies testing the effect of this variant on protein structure or activity have not been performed, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this to be a variant of uncertain significance. ACMG Criteria: PM2, PP3 |