Submissions for variant NM_004006.3(DMD):c.811C>T (p.Gln271Ter)

dbSNP: rs2063890662

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001251518	SCV001584665	pathogenic	Duchenne muscular dystrophy	2021-07-20	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 975106). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with clinical features of DMD-related conditions (PMID: 27593222). This sequence change creates a premature translational stop signal (p.Gln271*) 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). This variant is not present in population databases (ExAC no frequency).
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV001251518	SCV002769626	pathogenic	Duchenne muscular dystrophy	2022-12-16	criteria provided, single submitter	clinical testing	PVS1, PM2, PP5
Neuberg Centre For Genomic Medicine, NCGM	RCV001251518	SCV005438755	pathogenic	Duchenne muscular dystrophy	2023-07-22	criteria provided, single submitter	clinical testing	The observed stop gained c.811C>T p.Gln271Ter variant in DMD gene has been previously reported in multiple individuals affected with DMD-related muscular dystrophy Cho et al., 2017; Razeq and Ahmad, 2021; Peña-Padilla et al., 2021. It has also been observed to segregate with disease in related individuals Razeq and Ahmad, 2021; Peña-Padilla et al., 2021. The p.Gln271Ter variant is absent in gnomAD Exomes. This variant has been submitted to the ClinVar database as Pathogenic. The reference amino acid of p.Gln271Ter in DMD is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This sequence change creates a premature translational stop signal p.Gln271Ter in the DMD gene. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants in DMD gene have been previously reported to be disease causing Santos et al., 2014. For these reasons, this variant has been classified as Pathogenic.
Centro de Registro e Investigacion sobre Anomalias Congenitas, Hospital Civil de Guadalajara Dr. Juan I. Menchaca	RCV001251518	SCV001365404	pathogenic	Duchenne muscular dystrophy	2020-06-29	no assertion criteria provided	clinical testing	p.Gln271Ter variant in DMD has been observed in male Mexican patient one year old with very high hyperCKemia. This variant was absent from large population studies.