Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Istituto Neurologico Mediterraneo, |
RCV001250991 | SCV001424520 | likely pathogenic | Charcot-Marie-Tooth disease axonal type 2F | 2020-01-26 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001250991 | SCV002200640 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2F | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 190 of the HSPB1 protein (p.Gln190His). This variant is present in population databases (rs764297134, gnomAD 0.04%). This missense change has been observed in individual(s) with HSPB1-related conditions (PMID: 27492805, 31919945, 34354735). ClinVar contains an entry for this variant (Variation ID: 974685). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on HSPB1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |