Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000558745 | SCV000640206 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2F | 2019-05-13 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with phenylalanine at codon 77 of the HSPB1 protein (p.Leu77Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with an HSPB1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |