Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001051005 | SCV001215138 | uncertain significance | Duchenne muscular dystrophy | 2019-01-29 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with DMD-related conditions. This variant is present in population databases (rs367674503, ExAC 0.002%). This sequence change replaces threonine with alanine at codon 1692 of the DMD protein (p.Thr1692Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. |
Ambry Genetics | RCV003380819 | SCV004097127 | uncertain significance | Cardiovascular phenotype | 2023-07-05 | criteria provided, single submitter | clinical testing | The p.T1692A variant (also known as c.5074A>G), located in coding exon 36 of the DMD gene, results from an A to G substitution at nucleotide position 5074. The threonine at codon 1692 is replaced by alanine, an amino acid with similar properties. Based on data from gnomAD, the G allele has an overall frequency of 0.0005%% (1/182928) total alleles studied, with no hemizygotes observed. The highest observed frequency was 0.0012% (1/81505) of European (non-Finnish) alleles. This amino acid position is well 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. |
Natera, |
RCV001832469 | SCV002093542 | uncertain significance | Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency | 2021-06-24 | no assertion criteria provided | clinical testing |