Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Fulgent Genetics, |
RCV005011255 | SCV005636055 | uncertain significance | Kabuki syndrome 1; Choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome | 2024-04-28 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV005112555 | SCV005801288 | uncertain significance | Kabuki syndrome | 2024-03-16 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1199 of the KMT2D protein (p.Leu1199Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KMT2D-related conditions. This missense change has been observed in at least one individual who was not affected with KMT2D-related conditions (Invitae). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KMT2D protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |