Submissions for variant NM_004006.3(DMD):c.9G>A (p.Trp3Ter)

dbSNP: rs398122853

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000183395	SCV000112771	pathogenic	not provided	2017-04-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000183395	SCV000235849	pathogenic	not provided	2023-12-06	criteria provided, single submitter	clinical testing	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 in large population cohorts (gnomAD); Based on the understanding of this genetic alteration, it may be amenable to nonsense read-through therapy that is currently available or in clinical trial; This variant is associated with the following publications: (PMID: 21396098, 33420945, 27708273, 23757202, 19206170, 21399986, 31862442, 32453103, 31127727, 30190612, 32194622, 19793655, 12632325)
Athena Diagnostics	RCV000183395	SCV000255763	pathogenic	not provided	2018-09-04	criteria provided, single submitter	clinical testing	The variant creates a premature nonsense codon, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and not found in general population data.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000173322	SCV000550302	pathogenic	Duchenne muscular dystrophy	2024-08-07	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp3*) in the DMD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DMD are known to be pathogenic (PMID: 16770791, 25007885). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Becker muscular dystrophy (PMID: 12632325, 19793655, 21396098, 21399986). ClinVar contains an entry for this variant (Variation ID: 29962). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000173322	SCV001163464	pathogenic	Duchenne muscular dystrophy		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000183395	SCV001246675	pathogenic	not provided	2020-06-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001264540	SCV001442745	pathogenic	Qualitative or quantitative defects of dystrophin	2020-10-02	criteria provided, single submitter	clinical testing	Variant summary: DMD c.9G>A (p.Trp3X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 178651 control chromosomes. c.9G>A has been reported in the literature in multiple individuals affected with Dystrophinopathies, mainly as Becker Muscular Dystrophy (BMD) (example, Flanigan_2003, Flanigan_2009, Magri_2011, Reddy_2017). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in initiation of translation at downstream AUG codons within exon 6 leading to residual dystrophin expression (Gurvich_2009). Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000183395	SCV001762136	pathogenic	not provided	2021-06-17	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000183395	SCV002018594	pathogenic	not provided	2023-07-13	criteria provided, single submitter	clinical testing
MGZ Medical Genetics Center	RCV000022854	SCV002579359	pathogenic	Becker muscular dystrophy	2021-07-28	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000022854	SCV004194003	pathogenic	Becker muscular dystrophy	2022-12-31	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV000183395	SCV005413140	pathogenic	not provided	2024-06-21	criteria provided, single submitter	clinical testing
OMIM	RCV000022854	SCV000044145	pathogenic	Becker muscular dystrophy	2009-04-01	no assertion criteria provided	literature only
Counsyl	RCV000022854	SCV001132175	pathogenic	Becker muscular dystrophy	2019-07-11	no assertion criteria provided	clinical testing
Counsyl	RCV000984166	SCV001132176	pathogenic	Dilated cardiomyopathy 3B	2019-07-11	no assertion criteria provided	clinical testing
Counsyl	RCV000173322	SCV001132177	pathogenic	Duchenne muscular dystrophy	2019-07-11	no assertion criteria provided	clinical testing
Natera, Inc.	RCV001274389	SCV001458506	pathogenic	Dystrophin deficiency	2020-09-16	no assertion criteria provided	clinical testing