Submissions for variant NM_004006.3(DMD):c.5371C>T (p.Gln1791Ter)

dbSNP: rs1569559204

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000728336	SCV000855893	pathogenic	not provided	2017-07-27	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000728336	SCV000885304	pathogenic	not provided	2018-04-10	criteria provided, single submitter	clinical testing	The DMD c.5371C>T; p.Gln1791Ter variant has been reported in at least five muscular dystrophy patients, with diagnoses including Becker, Duchenne, and intermediate muscular dystrophy (Flanigan 2009, Juan-Mateu 2013). This variant introduces a premature termination codon in exon 38, and is expected to result in a truncated or absent protein product. Other truncating variants in exon 38 have been observed in cohorts of Duchenne and Becker muscular dystrophy patients (selected references: Flanigan 2009, Juan-Mateu 2013, Aartsma-Rus 2006). Based on the available information, the p.Gln1791Ter variant is classified as pathogenic.
Mendelics	RCV000990647	SCV001141664	pathogenic	Duchenne muscular dystrophy	2019-05-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000990647	SCV001580454	pathogenic	Duchenne muscular dystrophy	2020-01-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln1791*) in the DMD gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in DMD are known to be pathogenic (PMID: 16770791, 25007885). This variant has been observed in individual(s) with Becker, Duchenne, or intermediate muscular dystrophy (PMID: 19937601, 21972111, 23536893). ClinVar contains an entry for this variant (Variation ID: 593327). This variant is not present in population databases (ExAC no frequency).
Athena Diagnostics	RCV000728336	SCV001879913	pathogenic	not provided	2021-05-20	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been reported in patients with Becker muscular dystrophy (BMD), Duchenne muscular dystrophy (DMD), and an intermediate dystrophinopathy.
Neuberg Centre For Genomic Medicine, NCGM	RCV000990647	SCV005400754	pathogenic	Duchenne muscular dystrophy	2023-06-22	criteria provided, single submitter	clinical testing	The observed stop gained c.5371C>T(p.Gln1791Ter) variant in DMD gene has been reported previously in X-linked state in individual(s) affected with Becker, Duchenne, or intermediate muscular dystrophy (Juan-Mateu et al., 2013). This variant is absent in gnomAD Exomes. This variant has been reported to the ClinVar database as Pathogenic (multiple submitters). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DMD are known to be pathogenic (Santos et al., 2014). Computational evidence (MutationTaster - Disease causing automatic) predicts damaging effect on protein structure and function for this variant. For these reasons, this variant has been classified as Pathogenic.
Natera, Inc.	RCV001825446	SCV002093507	pathogenic	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2017-10-19	no assertion criteria provided	clinical testing