ClinVar Miner

Submissions for variant NM_004006.2(DMD):c.3232C>T (p.Leu1078Phe) (rs375329908)

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
Ambry Genetics RCV000618045 SCV000736339 uncertain significance Cardiovascular phenotype 2016-10-27 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000811104 SCV000951352 uncertain significance Duchenne muscular dystrophy 2019-11-21 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 1078 of the DMD protein (p.Leu1078Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs375329908, ExAC 0.01%). This variant has not been reported in the literature in individuals with DMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 518826). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Integrated Genetics/Laboratory Corporation of America RCV001194450 SCV001364023 uncertain significance not specified 2019-04-08 criteria provided, single submitter clinical testing Variant summary: DMD c.3232C>T (p.Leu1078Phe) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.7e-05 in 178540 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3232C>T in individuals affected with Dystrophinopathies and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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.