Submissions for variant NM_003482.4(KMT2D):c.15256C>T (p.Arg5086Ter)

dbSNP: rs727503979

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000153407	SCV000230779	pathogenic	not provided	2013-12-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000153407	SCV000680774	pathogenic	not provided	2025-01-02	criteria provided, single submitter	clinical testing	Identified in patients with Kabuki syndrome in published literature (PMID: 22126750, 36097644); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27302555, 36097644, 22126750)
Fulgent Genetics, Fulgent Genetics	RCV000178657	SCV000893299	pathogenic	Kabuki syndrome 1	2018-10-31	criteria provided, single submitter	clinical testing
3billion, Medical Genetics	RCV000178657	SCV002012256	pathogenic	Kabuki syndrome 1	2021-10-02	criteria provided, single submitter	clinical testing	Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant has been reported as pathogenic (ClinVar ID: VCV000167218.5). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003588580	SCV004295031	pathogenic	Kabuki syndrome	2023-06-15	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 167218). This premature translational stop signal has been observed in individual(s) with clinical features of Kabuki syndrome (PMID: 22126750). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg5086*) in the KMT2D gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KMT2D are known to be pathogenic (PMID: 22126750).
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000178657	SCV005200885	pathogenic	Kabuki syndrome 1	2024-06-18	criteria provided, single submitter	clinical testing	PVS1, PS4_Supporting, PM2
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000153407	SCV001808988	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000153407	SCV001927909	pathogenic	not provided		no assertion criteria provided	clinical testing