Submissions for variant NM_001540.5(HSPB1):c.452C>T (p.Thr151Ile)

dbSNP: rs28937568

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000809687	SCV000949853	pathogenic	Charcot-Marie-Tooth disease axonal type 2F	2024-01-22	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 151 of the HSPB1 protein (p.Thr151Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with distal hereditary motor neuropathy or Charcot-Marie-Tooth disease (PMID: 15122254, 18325928, 28144995, 29381233). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 7480). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HSPB1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001174177	SCV001337303	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001815164	SCV002062752	pathogenic	not provided	2022-03-01	criteria provided, single submitter	clinical testing
OMIM	RCV000007908	SCV000028113	pathogenic	Neuronopathy, distal hereditary motor, type 2B	2004-06-01	no assertion criteria provided	literature only