Submissions for variant NM_004006.3(DMD):c.3734C>T (p.Thr1245Ile)

gnomAD frequency: 0.01009  dbSNP: rs1800269

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080593	SCV000112495	benign	not specified	2015-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000080593	SCV000168178	benign	not specified	2013-10-14	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000080593	SCV000268957	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	p.Thr1245Ile in exon 27 of DMD: This variant is not expected to have clinical si gnificance because it has been identified in 1.1% (73/6728) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu /EVS/; dbSNP rs1800269).
PreventionGenetics, part of Exact Sciences	RCV000080593	SCV000309931	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000252057	SCV000318573	benign	Cardiovascular phenotype	2015-06-19	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.
Illumina Laboratory Services, Illumina	RCV000345231	SCV000482260	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000475998	SCV000560862	benign	Duchenne muscular dystrophy	2024-02-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001528847	SCV000885290	benign	not provided	2023-10-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000080593	SCV001339232	benign	not specified	2020-03-12	criteria provided, single submitter	clinical testing	Variant summary: DMD c.3734C>T (p.Thr1245Ile) results in a non-conservative amino acid change in 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 0.019 in 182401 control chromosomes, predominantly at a frequency of 0.089 within the Latino subpopulation in the gnomAD database, including 112 homozygotes and 971 hemizygotes. The observed variant frequency within Latino control individuals in the gnomAD database is significantly higher than expected for a pathogenic variant in DMD causing Dystrophinopathies phenotype, strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. Six ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Breakthrough Genomics, Breakthrough Genomics	RCV001528847	SCV005276022	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528847	SCV001741276	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000080593	SCV001800490	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000080593	SCV001923056	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001528847	SCV001931556	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001831846	SCV002085409	benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2017-04-21	no assertion criteria provided	clinical testing