ClinVar Miner

Submissions for variant NM_004006.3(DMD):c.4563G>A (p.Met1521Ile)

gnomAD frequency: 0.00003  dbSNP: rs138984555
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001215625 SCV001387379 uncertain significance Duchenne muscular dystrophy 2024-10-21 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1521 of the DMD protein (p.Met1521Ile). This variant is present in population databases (rs138984555, gnomAD 0.01%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 31983221). ClinVar contains an entry for this variant (Variation ID: 945083). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DMD protein function with a negative predictive value of 95%. 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 RCV002339563 SCV002636036 uncertain significance Cardiovascular phenotype 2020-10-27 criteria provided, single submitter clinical testing The p.M1521I variant (also known as c.4563G>A), located in coding exon 33 of the DMD gene, results from a G to A substitution at nucleotide position 4563. The methionine at codon 1521 is replaced by isoleucine, an amino acid with highly similar properties. Based on data from gnomAD, the A allele has an overall frequency of 0.002% (4/182467) total alleles studied, with 1 hemizygote observed. The highest observed frequency was 0.01% (1/7463) of Ashkenazi Jewish alleles. This amino acid position is not 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.
Revvity Omics, Revvity RCV003145398 SCV003829520 uncertain significance not provided 2019-06-24 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.