Submissions for variant NM_001540.5(HSPB1):c.277G>A (p.Asp93Asn)

gnomAD frequency: 0.00005  dbSNP: rs777201941

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000498200	SCV000590274	uncertain significance	not provided	2017-06-06	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the HSPB1 gene. The D93N variant has been reported previously as a variant of unknown significance in association with CMT; however, additional clinical information and inheritance pattern were not provided (DiVincenzo et al., 2014). The D93N variant is observed in 3/5180 (0.06%) alleles from individuals of European non-Finnish background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D93N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Aspartic acid are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae	RCV001084552	SCV000640208	likely benign	Charcot-Marie-Tooth disease axonal type 2F	2023-12-30	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001172550	SCV001335611	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing