Submissions for variant NM_001291415.2(KDM6A):c.3614G>A (p.Cys1205Tyr)

dbSNP: rs1556350571

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000690858	SCV000818587	likely pathogenic	Kabuki syndrome 2	2019-06-21	criteria provided, single submitter	clinical testing	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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed to be de novo in an individual with clinical features of KDM6A-related conditions (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 1153 of the KDM6A protein (p.Cys1153Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine.
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes	RCV000656306	SCV000778279	pathogenic	not provided	2017-08-14	no assertion criteria provided	clinical testing