Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000618045 | SCV000736339 | likely benign | Cardiovascular phenotype | 2024-08-27 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Labcorp Genetics |
RCV000811104 | SCV000951352 | uncertain significance | Duchenne muscular dystrophy | 2024-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1078 of the DMD protein (p.Leu1078Phe). This variant is present in population databases (rs375329908, gnomAD 0.02%). 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: 518826). 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. |
| Women's Health and 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. |
| Fulgent Genetics, |
RCV002477343 | SCV002790489 | uncertain significance | Becker muscular dystrophy; Duchenne muscular dystrophy; Dilated cardiomyopathy 3B | 2021-09-29 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001834964 | SCV002085476 | uncertain significance | Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency | 2018-06-26 | no assertion criteria provided | clinical testing |