Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000558745 | SCV000640206 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2F | 2023-11-14 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 77 of the HSPB1 protein (p.Leu77Phe). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with HSPB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 465268). 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. |
| MGZ Medical Genetics Center | RCV000558745 | SCV002579335 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2F | 2021-09-29 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002456125 | SCV002738149 | uncertain significance | Inborn genetic diseases | 2020-07-21 | criteria provided, single submitter | clinical testing | The p.L77F variant (also known as c.229C>T), located in coding exon 1 of the HSPB1 gene, results from a C to T substitution at nucleotide position 229. The leucine at codon 77 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |