Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001068128 | SCV001233218 | uncertain significance | Duchenne muscular dystrophy | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 1183 of the DMD protein (p.Arg1183Thr). This variant is present in population databases (rs374993642, gnomAD 0.01%). 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: 861572). 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. 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. |
ARUP Laboratories, |
RCV001811639 | SCV001472454 | uncertain significance | not provided | 2019-12-09 | criteria provided, single submitter | clinical testing | The DMD c.3548G>C; p.Arg1183Thr variant (rs374993642), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The arginine at codon 1183 is highly conserved, and computational analyses (SIFT: tolerated, PolyPhen-2: probably damaging) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Arg1183Thr variant is uncertain at this time. |
Ambry Genetics | RCV002339338 | SCV002619211 | uncertain significance | Cardiovascular phenotype | 2023-01-27 | criteria provided, single submitter | clinical testing | The p.R1183T variant (also known as c.3548G>C), located in coding exon 26 of the DMD gene, results from a G to C substitution at nucleotide position 3548. The arginine at codon 1183 is replaced by threonine, an amino acid with similar properties. Based on data from gnomAD, the C allele has an overall frequency of <0.01% (2/200582) total alleles studied, with 0 hemizygote(s) observed. The highest observed frequency was <0.01% (2/18499) of African alleles. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV001811639 | SCV003921534 | likely benign | not provided | 2023-04-27 | criteria provided, single submitter | clinical testing | See Variant Classification Assertion Criteria. |
Natera, |
RCV001827446 | SCV002085428 | uncertain significance | Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency | 2018-08-29 | no assertion criteria provided | clinical testing |