Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000390409 | SCV000361622 | uncertain significance | Imerslund-Grasbeck syndrome type 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 |
RCV001850578 | SCV002259121 | uncertain significance | Imerslund-Grasbeck syndrome | 2022-06-25 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 3140 of the CUBN protein (p.Ala3140Thr). This variant is present in population databases (rs148491916, gnomAD 0.04%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with CUBN-related conditions. ClinVar contains an entry for this variant (Variation ID: 299381). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; 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. |
| ARUP Laboratories, |
RCV003114471 | SCV003799695 | uncertain significance | not provided | 2022-03-16 | criteria provided, single submitter | clinical testing | The CUBN c.9418G>A, p.Ala3140Thr variant (rs148491916), to our knowledge, is not reported in the medical literature, but is reported in ClinVar (Variation ID: 299381). This variant is found in the general population with an overall allele frequency of 0.02% (53/282674 alleles) in the Genome Aggregation Database. The alanine at codon 3140 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.171). Due to limited information, the clinical significance of the p.Ala3140Thr variant is uncertain at this time. |
| Breakthrough Genomics, |
RCV003114471 | SCV005190654 | uncertain significance | not provided | criteria provided, single submitter | not provided | ||
| Department of Pathology and Laboratory Medicine, |
RCV000390409 | SCV005912714 | uncertain significance | Imerslund-Grasbeck syndrome type 1 | 2023-01-26 | criteria provided, single submitter | research |