Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000819893 | SCV000960578 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2019-12-30 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 3-12 of the LMNA gene. The 5' boundary is likely confined to intron 2. 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. A similar deletion of exons 3-12 has been reported in an individual affected with LMNA-related cardiac disease (PMID: 20127487). Variants that disrupt the p.Arg190 and p.Glu203 amino acid residues in exon 3 of LMNA have been observed in affected individuals (PMID: 16061563, 11897440, 22199124, 15219508, 26199943, 16537768, 20160190, 26899768, 18795223, 11561226, 22464770). This suggests that these are clinically significant residues, and that other variants that disrupt these residues are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |