ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.658C>T (p.Arg220Cys)

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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 RCV003067455 SCV003457527 uncertain significance Deficiency of alpha-mannosidase 2022-04-15 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 220 of the MAN2B1 protein (p.Arg220Cys). This variant is present in population databases (rs752541064, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with MAN2B1-related conditions. 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. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004587422 SCV005076821 uncertain significance not specified 2024-04-09 criteria provided, single submitter clinical testing Variant summary: MAN2B1 c.658C>T (p.Arg220Cys) results in a non-conservative amino acid change located in the Glycoside hydrolase family 38, N-terminal domain (IPR000602) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251462 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.658C>T in individuals affected with Alpha-Mannosidosis and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2150216). Based on the evidence outlined above, the variant was classified as uncertain significance.

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