Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000392411 | SCV000338309 | uncertain significance | not provided | 2018-04-23 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000377994 | SCV000482272 | uncertain significance | Dilated cardiomyopathy 3B | 2018-01-13 | 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 |
RCV001215920 | SCV001387689 | uncertain significance | Duchenne muscular dystrophy | 2024-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 716 of the DMD protein (p.Val716Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 285339). 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 | RCV002429226 | SCV002729298 | uncertain significance | Cardiovascular phenotype | 2023-05-26 | criteria provided, single submitter | clinical testing | The p.V716L variant (also known as c.2146G>C), located in coding exon 17 of the DMD gene, results from a G to C substitution at nucleotide position 2146. The valine at codon 716 is replaced by leucine, an amino acid with highly similar properties. Based on data from gnomAD, the C allele has an overall frequency of <0.01% (1/182635) total alleles studied, with 1 hemizygote observed. The highest observed frequency was <0.01% (1/81322) of European (non-Finnish) alleles. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Natera, |
RCV001828213 | SCV002092182 | uncertain significance | Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency | 2019-07-29 | no assertion criteria provided | clinical testing |