Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Medical Genetics and Applied Genomics, |
RCV001268118 | SCV001446778 | likely pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001880162 | SCV002231656 | pathogenic | Kabuki syndrome | 2021-06-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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. This variant has been observed in individual(s) with clinical features of Kabuki syndrome (PMID: 22126750, 30459467, 27302555). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 986938). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 5481 of the KMT2D protein (p.Cys5481Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. |