ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.1501T>A (p.Cys501Ser) (rs747721968)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001582678 SCV001821324 uncertain significance not specified 2021-08-20 criteria provided, single submitter clinical testing Variant summary: MAN2B1 c.1501T>A (p.Cys501Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250324 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1501T>A has been reported in the literature in an individual affected with Type II - Alpha-Mannosidosis. The individual was compound heterozygous for the variant of interest and another pathogenic variant. However, the variant was also in cis with another variant c.2849G>C p.R950P (Borgwardt_2015). Intra cellular processing, transport and secretion studies in cell culture suggested that single mutations p.C501S and p.R950P were processed and transported to lysosomes but in the combined double variant, no indication of lysosomal localization was noted. The authors further report that whether both mutations were required for the disease development remain unknown (Kuokkanen_2011). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000206970 SCV000243976 uncertain significance Deficiency of alpha-mannosidase 2012-06-07 no assertion criteria provided literature only

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