Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001071132 | SCV001236420 | likely pathogenic | Kabuki syndrome | 2019-04-02 | criteria provided, single submitter | clinical testing | This variant has been observed to be de novo in individuals affected with Kabuki syndrome (PMID: 21280141, 29846842). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 5210 of the KMT2D protein (p.Tyr5210Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). |