Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194223 | SCV001363585 | pathogenic | Beta-D-mannosidosis | 2019-08-05 | criteria provided, single submitter | clinical testing | Variant summary: MANBA c.1398G>A (p.Trp466X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. A splice site variant downstream of this position has been classified as pathogenic by our laboratory (c.2158-2A>G). The variant allele was found at a frequency of 4e-06 in 251454 control chromosomes. c.1398G>A has been reported in the literature in at-least one individual affected with Beta-Mannosidosis (Gort_2006). At least one publication reports experimental evidence evaluating an impact on protein function (Gort_2006). The most pronounced variant effect results in <10% of normal activity. 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 pathogenic. |
| Gene |
RCV004699186 | SCV005201560 | pathogenic | not provided | 2023-10-31 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 34426522, 18565776, 22369051, 19728872, 16904924) |
| Labcorp Genetics |
RCV001194223 | SCV005834945 | pathogenic | Beta-D-mannosidosis | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp466*) in the MANBA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MANBA are known to be pathogenic (PMID: 9384606, 12468273). This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with mannosidosis (PMID: 16904924). 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: 929155). For these reasons, this variant has been classified as Pathogenic. |