Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion, |
RCV001808187 | SCV002058752 | pathogenic | Duchenne muscular dystrophy | 2022-01-03 | criteria provided, single submitter | clinical testing | Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). The variant has been reported to be associated with DMD related disorder (PMID:8840119). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Mayo Clinic Laboratories, |
RCV003481132 | SCV004226196 | pathogenic | not provided | 2023-05-24 | criteria provided, single submitter | clinical testing | PP4, PM2, PS4_moderate, PVS1 |
| Labcorp Genetics |
RCV001808187 | SCV004298882 | pathogenic | Duchenne muscular dystrophy | 2023-06-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1333499). This variant is also known as del8290C (Phe2694fs). This premature translational stop signal has been observed in individual(s) with Duchenne or Becker muscular dystrophy (PMID: 8840119). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu2696Trpfs*30) in the DMD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DMD are known to be pathogenic (PMID: 16770791, 25007885). |
| Gene |
RCV003481132 | SCV005201812 | pathogenic | not provided | 2023-05-24 | criteria provided, single submitter | clinical testing | Reported previously in association with dystrophinopathy, most often with Duchenne muscular dystrophy, in published literature (Iskandar et al., 2022; Barbieri et al., 1996); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 36315559, 26147798, 8840119) |
| Victorian Clinical Genetics Services, |
RCV001808187 | SCV005398321 | pathogenic | Duchenne muscular dystrophy | 2024-10-08 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Becker muscular dystrophy (MIM#300376), Duchenne muscular dystrophy (MIM#310200) and dilated cardiomyopathy 3B (MIM#302045). (I) 0109 - This gene is associated with X-linked recessive disease. This gene is primarily associated with X-linked recessive disease relating to the muscular dystrophy phenotypes; however, it is also associated with X-linked DCM in heterozygous females (OMIM, GeneReviews, PMID: 26066469). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0253 - This variant is hemizygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. It has been identified in at least one hemizygous male with DMD (PMID: 36315559), and classified as pathogenic by diagnostic laboratories in ClinVar. (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |