Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV002470603 | SCV002768810 | uncertain significance | Kleefstra syndrome 2 | 2020-05-21 | criteria provided, single submitter | clinical testing | A heterozygous missense variant was identified, NM_170606.2(KMT2C):c.7170C>G in exon 37 of 59 of the KMT2C gene. This substitution is predicted to create a minor amino acid change from isoleucine to methionine at position 2390 of the protein, NP_733751.2(KMT2C):p.(Ile2390Met). The isoleucine at this position has moderate conservation (100 vertebrates, UCSC), but is not situated in a known functional domain. In silico software predictions of the pathogenicity of this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is not present in the gnomAD population database and has not been previously reported in clinical cases. Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS). |