Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV003448636 | SCV004176206 | uncertain significance | Kleefstra syndrome 2 | 2023-07-07 | criteria provided, single submitter | clinical testing | The c.14329C>T p.(Arg4777Trp) variant identified in the KMT2C gene substitutes a highly conserved Arginine for Tryptophan at amino acid 4777/4912 (exon 55/59). This variant is observed once as a heterozygous allele in population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. In silico predictions are in favor of the variant's damaging effect [REVEL = 0.866], however functional studies to support or refute these predictions have not been reported. Given the lack of compelling evidence for its pathogenicity, the c.14329C>T p.(Arg4777Trp) variant identified in the KMT2C gene is reported as a Variant of Uncertain Significance. |