Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000516728 | SCV000613676 | pathogenic | not provided | 2017-02-23 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000820858 | SCV000961590 | pathogenic | Charcot-Marie-Tooth disease axonal type 2F | 2019-04-15 | criteria provided, single submitter | clinical testing | This variant has been observed to be de novo in individuals affected with Charcot-Marie-Tooth disease, type 2 or distal hereditary motor neuropathy (PMID: 20870250, 28144995). This variant has also been observed in additional individuals affected with Charcot-Marie-Tooth disease, type 2 or distal hereditary motor neuropathy (PMID: 22176143, 26989944, 27862672). ClinVar contains an entry for this variant (Variation ID: 447531). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change results in an HSPB1 protein with a small increase of thermal stability, but without changes of chaperone-like activity (PMID: 25220807). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 180 of the HSPB1 protein (p.Thr180Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. |
Inherited Neuropathy Consortium | RCV000789962 | SCV000929347 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |