Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001101997 | SCV001258645 | uncertain significance | Hypermanganesemia with dystonia, polycythemia, and cirrhosis | 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. |
| Neuberg Centre For Genomic Medicine, |
RCV001101997 | SCV005329526 | uncertain significance | Hypermanganesemia with dystonia, polycythemia, and cirrhosis | 2023-05-20 | criteria provided, single submitter | clinical testing | The observed missense variant c.482G>T (p.Gly161Val) in SLC30A10 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Gly161Val variant is absent in gnomAD Exomes database. This variant has been submitted to the ClinVar database as Uncertain Significance. Multiple lines of computational evidence (SIFT - tolerated; Polyphen - benign; MutationTaster - polymorphism) predict no damaging effect on protein structure and function for this variant. The amino acid Gly at position 161 is changed to a Val changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS). In the absence of another reportable variant in the SLC30A10 gene, the molecular diagnosis is not confirmed. |