Submissions for variant NM_000521.4(HEXB):c.761T>C (p.Leu254Ser)

dbSNP: rs771103635

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000993713	SCV002246439	pathogenic	Sandhoff disease	2021-11-04	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. 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 HEXB protein function. ClinVar contains an entry for this variant (Variation ID: 800653). This missense change has been observed in individual(s) with Sandhoff disease (PMID: 33407268). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 254 of the HEXB protein (p.Leu254Ser).
Department of Pediatrics, Division of Medical Genetics, Faculty of Medicine Ramathibodi Hospital, Mahidol University	RCV000993713	SCV000999190	likely pathogenic	Sandhoff disease	2019-11-26	no assertion criteria provided	research	The patient showed classical presentation of with infantile onset Sandhoff disease plus deficient enzyme activity in leukocytes.