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

gnomAD frequency: 0.00001  dbSNP: rs771457306

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000599025	SCV000710125	uncertain significance	not provided	2022-07-26	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein elongation, as the last 15 amino acids are replaced with 35 different amino acids; Not observed at a significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV000795282	SCV000934734	uncertain significance	Charcot-Marie-Tooth disease axonal type 2F	2022-07-12	criteria provided, single submitter	clinical testing	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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 503828). This variant has not been reported in the literature in individuals affected with HSPB1-related conditions. This variant is present in population databases (rs771457306, gnomAD 0.004%). 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 15 amino acid(s) of the HSPB1 protein and extend the protein by 20 additional amino acid residues.
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