ClinVar Miner

Submissions for variant NM_001540.5(HSPB1):c.544C>G (p.Pro182Ala)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001217374 SCV001389210 pathogenic Charcot-Marie-Tooth disease axonal type 2F 2019-06-06 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 182 of the HSPB1 protein (p.Pro182Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with hereditary motor neuropathy in two families (PMID: 27816334, 29381233). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Pro182 amino acid residue in HSPB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18325928, 27816334, 29381233, 16155736, 25220807). 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.

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