Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000273131 | SCV000482247 | uncertain significance | Dilated cardiomyopathy 3B | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV000534069 | SCV000625913 | uncertain significance | Duchenne muscular dystrophy | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1683 of the DMD protein (p.Thr1683Pro). This variant is not present in population databases (gnomAD no frequency). 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: 368244). 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 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 | RCV003298417 | SCV004001551 | uncertain significance | Cardiovascular phenotype | 2023-03-24 | criteria provided, single submitter | clinical testing | The p.T1683P variant (also known as c.5047A>C), located in coding exon 36 of the DMD gene, results from an A to C substitution at nucleotide position 5047. The threonine at codon 1683 is replaced by proline, an amino acid with highly similar properties. 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. |
| Clinical Genomics Laboratory, |
RCV000273131 | SCV005685427 | uncertain significance | Dilated cardiomyopathy 3B | 2024-10-17 | criteria provided, single submitter | clinical testing | The DMD c.5047A>C (p.Thr1683Pro) variant, to our knowledge, has not been reported in the medical literature and is absent in the general population (gnomAD v.2.1.1), indicating that it is not a common variant. This variant was reported in the ClinVar database as a variant of uncertain significance by four submitters (ClinVar ID: 368244). Computational predictors indicate that this variant has no impact on DMD function. Due to limited information and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time. |
| Natera, |
RCV001273868 | SCV001457453 | uncertain significance | Dystrophin deficiency | 2020-09-16 | no assertion criteria provided | clinical testing |