Submissions for variant NM_019066.5(MAGEL2):c.1912C>T (p.Gln638Ter)

dbSNP: rs797044883

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000190699	SCV000244140	pathogenic	Inborn genetic diseases	2014-09-03	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000238706	SCV000297290	likely pathogenic	not provided	2015-12-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000762935	SCV000893358	pathogenic	Prader-Willi syndrome; Schaaf-Yang syndrome	2018-10-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000508676	SCV001158491	pathogenic	Schaaf-Yang syndrome	2019-06-26	criteria provided, single submitter	clinical testing
Center for Molecular Medicine, Children’s Hospital of Fudan University	RCV000508676	SCV001622604	pathogenic	Schaaf-Yang syndrome	2021-05-19	criteria provided, single submitter	clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV000508676	SCV002012480	pathogenic	Schaaf-Yang syndrome	2021-10-13	criteria provided, single submitter	research	ACMG codes: PVS1; PS4M; PM2; PP5
PreventionGenetics, part of Exact Sciences	RCV003407693	SCV004112089	pathogenic	MAGEL2-related disorder	2023-04-20	criteria provided, single submitter	clinical testing	The MAGEL2 c.1912C>T variant is predicted to result in premature protein termination (p.Gln638*). This variant was reported in multiple individuals with Schaaf-Yang syndrome and de novo occurrences have been noted in several cases (Urreizti et al. 2017. PubMed ID: 28281571; Halloun et al. 2021. PubMed ID: 34051361; Negishi et al. 2019. PubMed ID: 31791363). This variant was also reported in a patient with neonatal demise (Yang et al. 2019. PubMed ID: 31501239). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant has been interpreted as pathogenic and likely pathogenic by multiple submitters in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/208684/). Nonsense variants in MAGEL2 are expected to be pathogenic. This variant is interpreted as pathogenic.
GeneDx	RCV000238706	SCV004170148	pathogenic	not provided	2023-10-08	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation, as the last 612 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27195816, 31501239, 28281571, 31791363, 29359444, 34128869, 35595280, 34051361, 37404980, 33726816, 36243518)
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000508676	SCV004809925	pathogenic	Schaaf-Yang syndrome	2024-04-04	criteria provided, single submitter	clinical testing
OMIM	RCV000508676	SCV000605831	pathogenic	Schaaf-Yang syndrome	2017-09-26	no assertion criteria provided	literature only
Department Of Pediatrics And Neonatology, Nagoya City University Graduate School Of Medical Sciences	RCV000508676	SCV000784667	pathogenic	Schaaf-Yang syndrome	2018-06-25	no assertion criteria provided	clinical testing