ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.1345G>A (p.Val449Ile)

gnomAD frequency: 0.00001  dbSNP: rs764898305
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001890007 SCV002141656 uncertain significance Deficiency of alpha-mannosidase 2021-11-28 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 449 of the MAN2B1 protein (p.Val449Ile). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical suspicion of alpha mannosidosis (PMID: 32331969). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Breakthrough Genomics, Breakthrough Genomics RCV004693847 SCV005192605 uncertain significance not provided criteria provided, single submitter not provided

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