Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV001220792 | SCV000060906 | likely pathogenic | Desmin-related myofibrillar myopathy | 2017-05-22 | criteria provided, single submitter | clinical testing | The c.735+1G>A variant in DES has been reported in at least 2 individuals with d esminopathy (Shatunov et al., unpublished data; reviewed by Goldfarb 2004, Gudko va 2013, LMM data), and was absent from large population studies. This variant o ccurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Ad ditional variants affecting splicing of this exon have been reported in individu als with desminopathy including a different variant at the same position (c.7351 +G>C LMM data: variant occurred de novo) and c.735+3A>G (identified in 6 individ uals with desminopathy and segregated in 9 individuals from 2 families: Park 200 0, Dalakas 2000, Wahni 2012, Greenberg 2012, McDonald 2012, Gudkova 2013, LMM un published data). In summary, although additional studies are required to fully e stablish its clinical significance, the c.735+1G>A variant is likely pathogenic. |
| Eurofins Ntd Llc |
RCV000393713 | SCV000343204 | pathogenic | not provided | 2016-06-23 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001220792 | SCV001392803 | pathogenic | Desmin-related myofibrillar myopathy | 2024-05-18 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 3 of the DES gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with autosomal dominant DES-related conditions (PMID: 28703267, 30614851; Invitae). ClinVar contains an entry for this variant (Variation ID: 44268). Studies have shown that disruption of this splice site results in skipping of exon 3, but is expected to preserve the integrity of the reading-frame (PMID: 29034897, 30614851). For these reasons, this variant has been classified as Pathogenic. |
| Genomics England Pilot Project, |
RCV001220792 | SCV001760073 | likely pathogenic | Desmin-related myofibrillar myopathy | no assertion criteria provided | clinical testing |