Submissions for variant NM_000521.4(HEXB):c.1535_1536del (p.Arg512fs)

dbSNP: rs794727091

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724463	SCV000225797	pathogenic	not provided	2014-12-10	criteria provided, single submitter	clinical testing
Counsyl	RCV000174488	SCV000798302	likely pathogenic	Sandhoff disease	2018-03-06	criteria provided, single submitter	clinical testing
Invitae	RCV000174488	SCV000964142	pathogenic	Sandhoff disease	2023-12-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg512Thrfs*12) in the HEXB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 45 amino acid(s) of the HEXB protein. This variant is present in population databases (rs794727091, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with Sandhoff disease (PMID: 29448188). ClinVar contains an entry for this variant (Variation ID: 194180). This variant disrupts a region of the HEXB protein in which other variant(s) (p.Cys534*) have been determined to be pathogenic (PMID: 29448188, 30075786). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Daryl Scott Lab, Baylor College of Medicine	RCV000174488	SCV004102696	uncertain significance	Sandhoff disease	2023-11-10	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000174488	SCV002084953	likely pathogenic	Sandhoff disease	2021-01-10	no assertion criteria provided	clinical testing