ClinVar Miner

Submissions for variant NM_001540.5(HSPB1):c.380G>T (p.Arg127Leu) (rs587781250)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001048111 SCV001212100 pathogenic Charcot-Marie-Tooth disease axonal type 2F 2019-11-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 127 of the HSPB1 protein (p.Arg127Leu). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is present in population databases (rs587781250, ExAC 0.002%). This variant has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 25025039, 26675522). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 157529). This variant has been reported to affect HSPB1 protein function (PMID: 26675522). This variant disrupts the p.Arg127 amino acid residue in HSPB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15122254, 16215937, 20178975, 20660910, 21983720, 22031878, 23728742). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Molecular Genetics Laboratory,London Health Sciences Centre RCV000144874 SCV001337301 likely pathogenic Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Dept. of Medical Genetics, Telemark Hospital Trust RCV000144874 SCV000172146 pathogenic Charcot-Marie-Tooth disease 2013-11-01 no assertion criteria provided research

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