Submissions for variant NM_004006.3(DMD):c.2391T>G (p.Asn797Lys)

gnomAD frequency: 0.00714  dbSNP: rs72468681

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080498	SCV000112400	benign	not specified	2015-09-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000080498	SCV000168171	benign	not specified	2014-03-31	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
CSER _CC_NCGL, University of Washington	RCV000211534	SCV000212216	benign	Primary dilated cardiomyopathy	2015-03-11	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000080498	SCV000268951	benign	not specified	2015-03-12	criteria provided, single submitter	clinical testing	p.Asn797Lys in exon 20 of DMD: This variant is not expected to have clinical sig nificance because it has been identified in 1.2% (432/37288) European (Non-Finni sh) chromosomes by the Exome Aggregation Consortium Sequencing Project (http://e xac.broadinstitute.org/variant/X-32509625-A-C; dbSNP rs72468681). In addition, 5 individuals in this European cohort were homozygous and 141 were hemizygous fo r this variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081169	SCV000288049	benign	Duchenne muscular dystrophy	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000242843	SCV000318674	benign	Cardiovascular phenotype	2015-09-24	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756021	SCV000883723	benign	not provided	2023-08-09	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000756021	SCV000987367	likely benign	not provided		criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000211534	SCV000995799	benign	Primary dilated cardiomyopathy	2019-03-19	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001168045	SCV001330603	likely benign	Dilated cardiomyopathy 3B	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000080498	SCV001426846	benign	not specified	2020-07-09	criteria provided, single submitter	clinical testing	Variant summary: DMD c.2391T>G (p.Asn797Lys) results in a non-conservative amino acid change located in the Central rod domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0065 in 178379 control chromosomes, predominantly at a frequency of 0.011 within the Non-Finnish European subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 997 fold of the estimated maximal expected allele frequency for a pathogenic variant in DMD causing Dystrophinopathies phenotype (1.1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Eight ClinVar submitters (evaluation after 2014) cite the variant as benign (7x) and likely benign (1x). Based on the evidence outlined above, the variant was classified as benign.
Breakthrough Genomics, Breakthrough Genomics	RCV000756021	SCV005209200	likely benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000080498	SCV001739720	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000756021	SCV001799442	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000756021	SCV001924035	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000756021	SCV001929858	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000080498	SCV001970910	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001826735	SCV002089735	likely benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2017-04-20	no assertion criteria provided	clinical testing