Submissions for variant NM_004006.3(DMD):c.5899C>T (p.Arg1967Ter)

gnomAD frequency: 0.00001  dbSNP: rs128626249

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000711463	SCV000112577	pathogenic	not provided	2017-10-12	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000711463	SCV000841831	pathogenic	not provided	2017-09-19	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000012009	SCV001590857	pathogenic	Duchenne muscular dystrophy	2024-01-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1967*) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individuals with Duchenne or Becker muscular dystrophy (PMID: 8401539, 18652600, 30833962). This variant is also known as c.6107C>T. ClinVar contains an entry for this variant (Variation ID: 11258). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000711463	SCV001771076	pathogenic	not provided	2017-03-29	criteria provided, single submitter	clinical testing	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: 32559196, 31727011, 31919629, 30833962, 27363342, 19065519, 19937601, 19959795, 8401539, 18652600, 25525159, 15319032)
Revvity Omics, Revvity	RCV000711463	SCV002019345	pathogenic	not provided	2023-05-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002354155	SCV002653624	pathogenic	Cardiovascular phenotype	2020-12-30	criteria provided, single submitter	clinical testing	The p.R1967* pathogenic mutation (also known as c.5899C>T), located in coding exon 41 of the DMD gene, results from a C to T substitution at nucleotide position 5899. This changes the amino acid from an arginine to a stop codon within coding exon 41. This mutation has been detected in muscular dystrophy cohorts (Cunniff C et al. J Child Neurol, 2009 Apr;24:425-30; Takeshima Y et al. J Hum Genet, 2010 Jun;55:379-88; Park HJ et al. Clin Genet, 2017 03;91:403-410; Wang L et al. Front Genet, 2019 Feb;10:114; Okubo M et al. Hum Genet, 2020 Feb;139:247-255). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
OMIM	RCV000012009	SCV000032243	pathogenic	Duchenne muscular dystrophy	1993-01-01	no assertion criteria provided	literature only
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV000012009	SCV000747826	uncertain significance	Duchenne muscular dystrophy	2017-11-30	no assertion criteria provided	clinical testing	The observed variant c.5899C>T (p.Arg1967Ter) is not reported in 1000 Genomes and its minor allele frequency in ExAC databases is 0.00001328. The in silico prediction of the variant is disease causing by MutationTaster2.