Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV001089952 | SCV001245027 | uncertain significance | Kabuki syndrome 1 | 2018-11-12 | criteria provided, single submitter | clinical testing | A heterozygous missense variant, NM_003482.3(KMT2D):c.12637C>T, has been identified in exon 39 of 54 of the KMT2D gene. The variant is predicted to result in a moderate amino acid change from histidine to tyrosine at position 4213 of the protein (NP_003473.3(KMT2D):p.(His4213Tyr)). The histidine residue at this position has high conservation (100 vertebrates, UCSC), and is located within the atrophin 1 superfamily domain. In silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is absent in population databases (gnomAD, dbSNP, 1000G), and has not been previously reported in clinical cases. Analysis of parental samples indicated this variant is de novo, and is suspected to be in cis with the p.(Gln4090*) pathogenic variant. Based on the information available at the time of curation, this variant has been classified as VARIANT of UNCERTAIN SIGNIFICANCE (VUS). |