Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000802096 | SCV000941911 | uncertain significance | Beta-D-mannosidosis | 2022-08-15 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 847 of the MANBA protein (p.Thr847Asn). This variant is present in population databases (rs376012848, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with MANBA-related conditions. ClinVar contains an entry for this variant (Variation ID: 647562). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. |
| Illumina Laboratory Services, |
RCV000802096 | SCV001310574 | uncertain significance | Beta-D-mannosidosis | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Ambry Genetics | RCV002534697 | SCV003552699 | uncertain significance | Inborn genetic diseases | 2022-04-28 | criteria provided, single submitter | clinical testing | The c.2540C>A (p.T847N) alteration is located in exon 17 (coding exon 17) of the MANBA gene. This alteration results from a C to A substitution at nucleotide position 2540, causing the threonine (T) at amino acid position 847 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |