Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001248477 | SCV001421965 | uncertain significance | Duchenne muscular dystrophy | 2022-07-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 314 of the DMD protein (p.Arg314Leu). 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: 972442). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
Athena Diagnostics Inc | RCV001288598 | SCV001475846 | uncertain significance | not provided | 2020-03-16 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002375306 | SCV002687147 | uncertain significance | Cardiovascular phenotype | 2021-11-01 | criteria provided, single submitter | clinical testing | The p.R314L variant (also known as c.941G>T), located in coding exon 9 of the DMD gene, results from a G to T substitution at nucleotide position 941. The arginine at codon 314 is replaced by leucine, an amino acid with dissimilar properties. Based on data from gnomAD, the T allele has an overall frequency of 0.002% (3/181635) total alleles studied, with 1 hemizygote observed. The highest observed frequency was 0.004% (3/80937) of non-Finnish European 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. |
Natera, |
RCV001836249 | SCV002090439 | uncertain significance | Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency | 2019-04-11 | no assertion criteria provided | clinical testing |