ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.598C>A (p.His200Asn)

gnomAD frequency: 0.00001  dbSNP: rs772108001
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000206941 SCV002193375 pathogenic Deficiency of alpha-mannosidase 2022-09-17 criteria provided, single submitter clinical testing This variant is present in population databases (rs772108001, gnomAD 0.003%). This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 200 of the MAN2B1 protein (p.His200Asn). This missense change has been observed in individual(s) with alpha mannosidosis (PMID: 16919251, 22161967, 26048034). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 208255). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects MAN2B1 function (PMID: 16919251, 21505070, 22161967). This variant disrupts the p.His200 amino acid residue in MAN2B1. Other variant(s) that disrupt this residue have been observed in individuals with MAN2B1-related conditions (PMID: 22161967, 26048034), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000206941 SCV004191919 likely pathogenic Deficiency of alpha-mannosidase 2022-07-13 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000206941 SCV005655515 likely pathogenic Deficiency of alpha-mannosidase 2024-02-27 criteria provided, single submitter clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000206941 SCV000243961 not provided Deficiency of alpha-mannosidase no assertion provided literature only
Counsyl RCV000206941 SCV000797518 uncertain significance Deficiency of alpha-mannosidase 2018-02-05 flagged submission clinical testing

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