Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001786457 | SCV002028743 | likely pathogenic | not provided | 2024-08-18 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate reduced secreted protein expression and significantly decreased enzyme activity compared to wild-type (PMID: 19728872, 30552791); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22369051, 18980795, 30552791, 19728872, 30548430) |
Labcorp Genetics |
RCV001264746 | SCV002150396 | uncertain significance | Beta-D-mannosidosis | 2024-09-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 641 of the MANBA protein (p.Arg641His). This variant is present in population databases (rs569997475, gnomAD 0.05%). This missense change has been observed in individual(s) with beta-mannosidosis (PMID: 18980795). ClinVar contains an entry for this variant (Variation ID: 975740). Invitae Evidence 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 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 MANBA protein function. Experimental studies have shown that this missense change affects MANBA function (PMID: 19728872, 30552791). 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, |
RCV001264746 | SCV005380543 | likely pathogenic | Beta-D-mannosidosis | 2024-08-20 | criteria provided, single submitter | clinical testing | Variant summary: MANBA c.1922G>A (p.Arg641His) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00013 in 251248 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in MANBA causing Beta-Mannosidosis (0.00013 vs 0.0011), allowing no conclusion about variant significance. c.1922G>A has been reported in the literature in at-least one homozygous individual affected with Beta-Mannosidosis (example: Labauge_2009). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity in eukaryotic cells (Sabourdy_2009). The following publications have been ascertained in the context of this evaluation (PMID: 22369051, 18980795, 19728872). ClinVar contains an entry for this variant (Variation ID: 975740). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Fulgent Genetics, |
RCV001264746 | SCV005659884 | uncertain significance | Beta-D-mannosidosis | 2024-01-19 | criteria provided, single submitter | clinical testing | |
Centre de Biologie Pathologie Génétique, |
RCV001252566 | SCV001428324 | likely benign | Intellectual disability | 2019-01-01 | no assertion criteria provided | clinical testing | |
Department of Genetics, |
RCV001264746 | SCV001442980 | likely pathogenic | Beta-D-mannosidosis | 2020-04-22 | no assertion criteria provided | clinical testing | |
Center for Computational Biology & Bioinformatics, |
RCV004570645 | SCV005049952 | uncertain significance | Meniere disease | 2024-06-03 | no assertion criteria provided | research |