Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV004799323 | SCV001431140 | uncertain significance | Kleefstra syndrome 2 | 2019-12-15 | criteria provided, single submitter | clinical testing | The c.11843A>C (p.Gln3948Pro) variant identified substitutes a well conserved Glutamine for Proline at amino acid 3948/4912 (coding exon 46/59). This variant is absent from gnomAD, suggesting it is not a common benign variant in the populations represented in this database. In silico algorithms do not agree on the effect of this variant, as it is predicted both Deleterious (Provean; score: -2.58) and Tolerated (SIFT; score: 0.162) to the function of the canonical transcript. To our current knowledge this variant has not been reported in affected individuals in the literature. While the majority of pathogenic variants in KMT2C are nonsense or frameshift [PMID: 29069077; PMID: 29276005], missense variants have been described in individuals with clinical symptoms consistent with Kleefstra syndrome [PMID: 29276005], and missense variants have been reported in ClinVar as Likely Pathogenic. |
| Gene |
RCV003128770 | SCV003805039 | uncertain significance | not provided | 2022-08-14 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |