Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001139358 | SCV001299500 | uncertain significance | Sitosterolemia 1 | 2018-01-12 | 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 |
RCV001882423 | SCV002165551 | uncertain significance | not provided | 2022-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 462 of the ABCG8 protein (p.Asn462Ser). This variant is present in population databases (rs769333089, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ABCG8-related conditions. ClinVar contains an entry for this variant (Variation ID: 896597). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Ambry Genetics | RCV003163306 | SCV003912014 | uncertain significance | Cardiovascular phenotype | 2022-11-17 | criteria provided, single submitter | clinical testing | The p.N462S variant (also known as c.1385A>G), located in coding exon 9 of the ABCG8 gene, results from an A to G substitution at nucleotide position 1385. The asparagine at codon 462 is replaced by serine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Zotz- |
RCV001139358 | SCV004171662 | uncertain significance | Sitosterolemia 1 | 2023-11-24 | no assertion criteria provided | clinical testing |