Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000641086 | SCV000762704 | likely pathogenic | Charcot-Marie-Tooth disease axonal type 2F | 2017-12-01 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 2-3 of the HSPB1 gene. The 5' boundary is likely confined to intron 1. 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 variant has not been reported in individuals affected with HSPB1-related disorders. A different variant (p.Q175*) that results in the truncation of the last 30 amino acids of the HSPB1 protein has been determined to be pathogenic (PMID: 22734906, 28144995). This suggests that other variants that result in C-terminal truncations may also be pathogenic. 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. |