Submissions for variant NM_000528.4(MAN2B1):c.1259G>T (p.Gly420Val)

gnomAD frequency: 0.00001  dbSNP: rs772853856

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000206944	SCV002307333	uncertain significance	Deficiency of alpha-mannosidase	2022-10-22	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 420 of the MAN2B1 protein (p.Gly420Val). This variant is present in population databases (rs772853856, gnomAD 0.01%). This missense change has been observed in individual(s) with leukodystrophy (PMID: 17404523). ClinVar contains an entry for this variant (Variation ID: 208264). 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 not expected to disrupt MAN2B1 protein function. Experimental studies have shown that this missense change affects MAN2B1 function (PMID: 21505070, 22161967). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics	RCV000206944	SCV002800862	uncertain significance	Deficiency of alpha-mannosidase	2022-05-07	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000206944	SCV004191869	likely pathogenic	Deficiency of alpha-mannosidase	2023-07-26	criteria provided, single submitter	clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000206944	SCV000243970	uncertain significance	Deficiency of alpha-mannosidase	2012-06-07	no assertion criteria provided	literature only