Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001217598 | SCV001389444 | uncertain significance | Duchenne muscular dystrophy | 2022-07-05 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 2915 of the DMD protein (p.Trp2915Cys). This variant is present in population databases (rs761750882, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 946689). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. |
Ambry Genetics | RCV003380890 | SCV004097144 | uncertain significance | Cardiovascular phenotype | 2023-08-30 | criteria provided, single submitter | clinical testing | The p.W2915C variant (also known as c.8745G>T), located in coding exon 59 of the DMD gene, results from a G to T substitution at nucleotide position 8745. The tryptophan at codon 2915 is replaced by cysteine, an amino acid with highly dissimilar properties. Based on data from gnomAD, the T allele has an overall frequency of 0.0011% (2/183302) total alleles studied, with 1 hemizygote(s) observed. The highest observed frequency was 0.0072% (1/13857) of East 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. |
Natera, |
RCV001828730 | SCV002080245 | uncertain significance | Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency | 2018-11-23 | no assertion criteria provided | clinical testing |