Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000468008 | SCV000551567 | likely pathogenic | Charcot-Marie-Tooth disease axonal type 2F | 2016-11-06 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the last exon of the HSPB1 mRNA at codon 175 (p.Gln175*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 31 amino acids of the HSPB1 protein. This variant is not present in population databases (ExAC no frequency). A different variant (c.523C>T) giving rise to the same protein effect observed here (p.Gln175*) has been reported to segregate with Charcot-Marie-Tooth disease type 2 (CMT2) in an affected family (PMID: 22734906), indicating that the truncated residues may be critical for protein function. In summary, this is a novel truncating variant that is likely to disrupt HSPB1 protein function. However, additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |