Submissions for variant NM_004006.3(DMD):c.5785G>C (p.Val1929Leu)

gnomAD frequency: 0.00001  dbSNP: rs794729004

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000183417	SCV000235876	uncertain significance	not provided	2014-07-17	criteria provided, single submitter	clinical testing	p.Val1929Leu (GTG>CTG): c.5785 G>C in exon 41 of the DMD gene (NM_004006.2). A variant of unknown significance has been identified in the DMD gene. The V1929L variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The V1929L variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The V1929L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Moreover, no missense mutations in nearby residues have been reported in association with DMD/BMD, indicating that this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).
Labcorp Genetics (formerly Invitae), Labcorp	RCV003765138	SCV004644673	uncertain significance	Duchenne muscular dystrophy	2023-03-07	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DMD protein function. ClinVar contains an entry for this variant (Variation ID: 201752). This variant has not been reported in the literature in individuals affected with DMD-related conditions. This variant is present in population databases (rs794729004, gnomAD 0.004%). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1929 of the DMD protein (p.Val1929Leu).
Natera, Inc.	RCV001827987	SCV002093456	uncertain significance	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2020-08-28	no assertion criteria provided	clinical testing