Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000198307 | SCV000254742 | uncertain significance | Charcot-Marie-Tooth disease type 2F | 2018-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 204 of the HSPB1 protein (p.Ala204Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs367857772, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with an HSPB1-related disease. ClinVar contains an entry for this variant (Variation ID: 216545). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on HSPB1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Fulgent Genetics, |
RCV000765975 | SCV000897397 | uncertain significance | Charcot-Marie-Tooth disease type 2F; Distal hereditary motor neuronopathy type 2B | 2018-10-31 | criteria provided, single submitter | clinical testing |