Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001204983 | SCV001376217 | pathogenic | Duchenne muscular dystrophy | 2019-09-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in DMD are known to be pathogenic (PMID: 16770791, 25007885). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in an individual affected with Duchenne muscular dystrophy (PMID: 19783145). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln1885*) in the DMD gene. It is expected to result in an absent or disrupted protein product. |
| Mendelics | RCV002249793 | SCV002519532 | pathogenic | Becker muscular dystrophy | 2022-05-04 | criteria provided, single submitter | clinical testing | |
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RCV001204983 | SCV003925056 | pathogenic | Duchenne muscular dystrophy | criteria provided, single submitter | clinical testing | A Hemixygote, Nonsense variant c.5629C>T in Exon 40 of the DMD gene that results in the amino acid substitution p.Gln1877* was identified. The observed variant has a maximum allele frequency of 0.00% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score. Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic (Variation ID: 936227). The variant has been reported in a patient with DMD (Torella A et al.,2020). Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines. |