Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000809687 | SCV000949853 | pathogenic | Charcot-Marie-Tooth disease axonal type 2F | 2018-09-10 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 151 of the HSPB1 protein (p.Thr151Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with distal hereditary motor neuropathy in a family (PMID: 15122254, 18325928), and has also been observed in additional families and individuals affected with distal hereditary motor neuropathy or Charcot-Marie-Tooth disease (PMID: 28144995, 29381233). ClinVar contains an entry for this variant (Variation ID: 7480). 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. For these reasons, this variant has been classified as Pathogenic. |
Molecular Genetics Laboratory, |
RCV001174177 | SCV001337303 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
OMIM | RCV000007908 | SCV000028113 | pathogenic | Distal hereditary motor neuronopathy type 2B | 2004-06-01 | no assertion criteria provided | literature only |