ClinVar Miner

Submissions for variant NM_001540.5(HSPB1):c.572_584del (p.Leu191fs) (rs771457306)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599025 SCV000710125 uncertain significance not provided 2017-11-17 criteria provided, single submitter clinical testing The c.572_584del13 variant in the HSPB1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.572_584del13 variant causes a frameshift starting with codon Leucine 191, changes this amino acid to a Glutamine residue, and creates a premature Stop codon at position 36 of the new reading frame, denoted p.Leu191GlnfsX36. This frameshift variant replaces the typical last 15 amino acid residues in the HSPB1 protein with 35 different amino acid residues. This change is expected to alter the normal structure and function of the resultant protein. The c.572_584del13 variant is observed in 4/108566 (0.004%) alleles from individuals of non-Finnish European background in large population cohorts (Lek et al., 2016). We interpret c.572_584del13 as a variant of uncertain significance.
Invitae RCV000795282 SCV000934734 uncertain significance Charcot-Marie-Tooth disease axonal type 2F 2018-09-12 criteria provided, single submitter clinical testing This sequence change results in a frameshift in the HSPB1 gene (p.Leu191Glnfs*36). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 36 amino acids of the HSPB1 protein and extend the protein by an additional 21 amino acids. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with HSPB1-related disease. ClinVar contains an entry for this variant (Variation ID: 503828). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. 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.
Molecular Genetics Laboratory,London Health Sciences Centre RCV000857187 SCV001335612 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Genesis Genome Database RCV000857187 SCV000999769 uncertain significance Charcot-Marie-Tooth disease 2019-08-14 no assertion criteria provided research

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