Submissions for variant NM_000528.4(MAN2B1):c.215A>T (p.His72Leu)

dbSNP: rs387906261

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000001752	SCV001581395	pathogenic	Deficiency of alpha-mannosidase	2023-09-25	criteria provided, single submitter	clinical testing	This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 72 of the MAN2B1 protein (p.His72Leu). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects MAN2B1 function (PMID: 15035660, 26817023). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MAN2B1 protein function. ClinVar contains an entry for this variant (Variation ID: 1684). This missense change has been observed in individual(s) with alpha-mannosidosis (PMID: 9158146; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency).
Genome-Nilou Lab	RCV000001752	SCV002014520	likely pathogenic	Deficiency of alpha-mannosidase	2021-09-05	criteria provided, single submitter	clinical testing
OMIM	RCV000001752	SCV000021908	pathogenic	Deficiency of alpha-mannosidase	1998-10-01	no assertion criteria provided	literature only
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000001752	SCV000243988	uncertain significance	Deficiency of alpha-mannosidase	2012-06-07	no assertion criteria provided	literature only