ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.788C>T (p.Pro263Leu)

gnomAD frequency: 0.00001  dbSNP: rs746808159
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206987 SCV001227594 likely pathogenic Deficiency of alpha-mannosidase 2024-01-20 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 263 of the MAN2B1 protein (p.Pro263Leu). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with alpha-mannosidosis (PMID: 22161967, 24353136). 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: 208259). 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. Experimental studies have shown that this missense change affects MAN2B1 function (PMID: 22161967). 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.
Baylor Genetics RCV000206987 SCV004191866 likely pathogenic Deficiency of alpha-mannosidase 2023-08-02 criteria provided, single submitter clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000206987 SCV000243965 uncertain significance Deficiency of alpha-mannosidase 2012-06-07 no assertion criteria provided literature only
Natera, Inc. RCV000206987 SCV001454362 likely pathogenic Deficiency of alpha-mannosidase 2020-09-16 no assertion criteria provided clinical testing

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