ClinVar Miner

Submissions for variant NM_001540.5(HSPB1):c.539C>T (p.Thr180Ile) (rs1422978230)

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Total submissions: 3
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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 type 2F 2018-09-17 criteria provided, single submitter clinical testing 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. This variant is not present in population databases (ExAC no frequency). 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). 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). For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789962 SCV000929347 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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