Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000183422 | SCV000235881 | uncertain significance | not provided | 2014-09-03 | criteria provided, single submitter | clinical testing | p.Arg751Trp (CGG>TGG): c.2251 C>T in exon 18 of the DMD gene (NM_004006.2). A variant of unknown significance has been identified in the DMD gene. The R751W variant has not been published as a mutation or as a benign polymorphism to our knowledge. The R751W variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The R571W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In addition, this substitution occurs at a position that is conserved across species. Moreover, in silico analysis predicts this variant is probably damaging to the protein structure/function. However, no missense mutations in nearby residues have been reported in association with DMD-related disorder, indicating this region of the protein may be tolerant of change. Finally, the majority of disease-causing mutations in the DMD gene are exon-level deletions or duplications. 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). |
Blueprint Genetics | RCV000208236 | SCV000263832 | uncertain significance | Primary dilated cardiomyopathy | 2015-08-10 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001464816 | SCV001668791 | likely benign | Duchenne muscular dystrophy | 2024-01-18 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004020213 | SCV005021721 | uncertain significance | Cardiovascular phenotype | 2023-12-22 | criteria provided, single submitter | clinical testing | The p.R751W variant (also known as c.2251C>T), located in coding exon 18 of the DMD gene, results from a C to T substitution at nucleotide position 2251. The arginine at codon 751 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration has been reported in a Duchenne muscular dystrophy cohort (Kumar SH et al. PLoS One, 2020 Jun;15:e0232654). Based on data from gnomAD, the T allele has an overall frequency of <0.01% (8/183160) total alleles studied, with 4 hemizygotes observed. The highest observed frequency was 0.03% (5/19037) of South Asian alleles. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |