Submissions for variant NM_003482.4(KMT2D):c.6295C>T (p.Arg2099Ter)

dbSNP: rs1452715535

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000622445	SCV000741406	pathogenic	Inborn genetic diseases	2016-03-21	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659734	SCV000781582	pathogenic	Kabuki syndrome 1	2016-11-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000760463	SCV000890350	pathogenic	not provided	2018-08-17	criteria provided, single submitter	clinical testing	The R2099X variant in the KMT2D gene has been reported in association with Kabuki syndrome (Ng et al., 2010; Micale et al., 2011; Banka et al., 2012; Bögershausen et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R2099X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R2099X as a pathogenic variant.
Diagnostic Laboratory, Strasbourg University Hospital	RCV001257646	SCV001434456	pathogenic	Intellectual disability	2020-04-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000760463	SCV001500529	pathogenic	not provided	2020-10-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004533293	SCV004719747	pathogenic	KMT2D-related disorder	2024-01-15	criteria provided, single submitter	clinical testing	The KMT2D c.6295C>T variant is predicted to result in premature protein termination (p.Arg2099*). This variant was reported de novo in individuals with Kabuki syndrome (Table S3, Ng et al. 2010. PubMed ID: 20711175; Mellis et al. 2021. PubMed ID: 34411415; Table S1, Levy et al. 2022. PubMed ID: 35904121; Table S2, Butcher et al. 2017. PubMed ID: 28475860; Cocciadiferro et al. 2018. PubMed ID: 30107592; Murakami et al. 2020. PubMed ID: 32803813). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in KMT2D are expected to be pathogenic. This variant is interpreted as pathogenic.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV000659734	SCV001427783	pathogenic	Kabuki syndrome 1	2019-01-01	no assertion criteria provided	clinical testing
Autoinflammatory diseases unit, CHU de Montpellier	RCV000659734	SCV001438179	pathogenic	Kabuki syndrome 1	2014-02-10	no assertion criteria provided	clinical testing
OMIM	RCV000659734	SCV003840914	pathogenic	Kabuki syndrome 1	2023-01-04	no assertion criteria provided	literature only
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV000659734	SCV004041703	pathogenic	Kabuki syndrome 1	2023-10-09	no assertion criteria provided	clinical testing