Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000708338 | SCV000837448 | likely pathogenic | Charcot-Marie-Tooth disease type 2 | 2018-02-08 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 10 to 12 of the LMNA gene. The 5' boundary is likely confined to intron 10. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. This deletion has not been reported in the literature in individuals affected with LMNA-related conditions. Missense substitutions of residue p.Arg541 in exon 10, within the region deleted by this variant , have been determined to be pathogenic (PMID: PMID:14675861, 14684700, 18646565,24623722, 22186027).  This suggests that deletion of this region of the LMNA protein is causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |