Submissions for variant NM_004006.3(DMD):c.5771_5772del (p.Glu1924fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002308654	SCV002600703	pathogenic	Qualitative or quantitative defects of dystrophin	2022-10-03	criteria provided, single submitter	clinical testing	Variant summary: DMD c.5771_5772delAG (p.Glu1924GlyfsX7) 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 and associated with DMD phenotype in HGMD. The variant was absent in 182573 control chromosomes. c.5771_5772delAG has been reported in the literature in individuals clinically diagnosed with Duchenne muscular dystrophy (DMD)(example Almomani_2009, Buzin 2005 and Flanigan_2009 etc.). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003102291	SCV003445057	pathogenic	Duchenne muscular dystrophy	2023-01-07	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1723378). This premature translational stop signal has been observed in individual(s) with Duchenne muscular dystrophy (PMID: 15643612, 19409785). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu1924Glyfs*7) 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).