Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000684870 | SCV000812331 | likely pathogenic | Charcot-Marie-Tooth disease axonal type 2F | 2022-07-18 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Ser135 amino acid residue in HSPB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15122254, 18832141, 23963299, 27816334). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HSPB1 protein function. ClinVar contains an entry for this variant (Variation ID: 565333). This missense change has been observed in individual(s) with clinical features of HSPB1-related conditions (PMID: 32397312). This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 135 of the HSPB1 protein (p.Ser135Ala). This variant is present in population databases (rs766728475, gnomAD 0.002%). |