Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001149360 | SCV001310306 | uncertain significance | Fanconi-Bickel syndrome | 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. |
| Labcorp Genetics |
RCV001149360 | SCV002188297 | uncertain significance | Fanconi-Bickel syndrome | 2022-03-22 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 902647). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC2A2 protein function. This variant has not been reported in the literature in individuals affected with SLC2A2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 174 of the SLC2A2 protein (p.Met174Thr). |
| Fulgent Genetics, |
RCV002483879 | SCV002786850 | uncertain significance | Type 2 diabetes mellitus; Fanconi-Bickel syndrome | 2024-05-03 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004751895 | SCV005351379 | uncertain significance | SLC2A2-related disorder | 2024-05-28 | no assertion criteria provided | clinical testing | The SLC2A2 c.2T>C variant is predicted to disrupt the translation initiation site (Start loss). This variant is predicted to disrupt the translation initiation site (start loss) in a non-canonical transcript (NM_00127859.1). In the canonical transcript (NM_000340.2), this variant results in a missense change (c.521T>C, p.Met174Thr). To our knowledge, this variant has not been previously reported in association with disease. This variant is reported in 0.0055% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |