ClinVar Miner

Submissions for variant NM_001540.5(HSPB1):c.257C>T (p.Ser86Leu) (rs749378020)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000530085 SCV000640207 uncertain significance Charcot-Marie-Tooth disease type 2F 2017-06-13 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 86 of the HSPB1 protein (p.Ser86Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. While this variant is present in population databases (rs749378020), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in the homozygous state in two siblings from a consanguineous family, one of whom was affected with distal hereditary motor neuropathy while the other was affected with amyotrophic lateral sclerosis (PMID: 26768280). 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: "Tolerated"; 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.