Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001247542 | SCV001420970 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2F | 2023-08-24 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with HSPB1-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 971702). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 88 of the HSPB1 protein (p.Ile88Met). |
| Ambry Genetics | RCV002451613 | SCV002739413 | uncertain significance | Inborn genetic diseases | 2021-02-23 | criteria provided, single submitter | clinical testing | The p.I88M variant (also known as c.264C>G), located in coding exon 1 of the HSPB1 gene, results from a C to G substitution at nucleotide position 264. The isoleucine at codon 88 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |