Submissions for variant NM_000521.4(HEXB):c.1169+3_1169+10del

dbSNP: rs398123444

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079055	SCV000110924	uncertain significance	not provided	2012-08-10	criteria provided, single submitter	clinical testing
Invitae	RCV001028022	SCV001575799	likely pathogenic	Sandhoff disease	2020-03-12	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 9 of the HEXB gene. It does not directly change the encoded amino acid sequence of the HEXB protein, but it affects a nucleotide within the consensus splice site of the intron. This variant has been observed in individual(s) with Sandhoff disease (PMID: 21567908, 27629047, Invitae). ClinVar contains an entry for this variant (Variation ID: 93195). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies.
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV001028022	SCV001190786	pathogenic	Sandhoff disease	2020-02-05	no assertion criteria provided	clinical testing
Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)	RCV001028022	SCV003927887	pathogenic	Sandhoff disease	2023-04-01	no assertion criteria provided	clinical testing