ClinVar Miner

Submissions for variant NM_001540.5(HSPB1):c.403T>G (p.Ser135Ala) (rs766728475)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000684870 SCV000812331 uncertain significance Charcot-Marie-Tooth disease axonal type 2F 2018-05-11 criteria provided, single submitter clinical testing This sequence change replaces serine with alanine at codon 135 of the HSPB1 protein (p.Ser135Ala). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and alanine. This variant is present in population databases (rs766728475, ExAC 0.003%). This variant has not been reported in the literature in individuals with HSPB1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). The p.Ser135 amino acid residue in HSPB1 has been determined to be clinically significant (PMID: 15122254, 18832141, 23963299, 27816334). This suggests that variants that disrupt this residue are likely to be causative of disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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