Submissions for variant NM_004006.3(DMD):c.354G>A (p.Trp118Ter)

dbSNP: rs2148849959

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001868836	SCV002245641	pathogenic	Duchenne muscular dystrophy	2022-08-09	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Duchenne muscular dystrophy (PMID: 20485447). ClinVar contains an entry for this variant (Variation ID: 1322326). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Trp118*) 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).
Neuberg Centre For Genomic Medicine, NCGM	RCV001868836	SCV004048203	likely pathogenic	Duchenne muscular dystrophy		criteria provided, single submitter	clinical testing	The variant c.354G>A (p.Trp118Ter) in DMD gene has been reported previously in patients affected with DMD (Liu, Yedan, et al). The p.Trp118Ter variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to ClinVar database as pathogenic. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. The nucleotide change in DMD is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic