Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Clinical Services Laboratory, |
RCV000261598 | SCV000452051 | uncertain significance | APC-Associated Polyposis Disorders | 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. |
| Invitae | RCV000463001 | SCV000552550 | likely benign | Familial adenomatous polyposis 1 | 2019-11-22 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000478957 | SCV000565713 | uncertain significance | not provided | 2016-09-06 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.7903A>G at the cDNA level, p.Thr2635Ala (T2635A) at the protein level, and results in the change of a Threonine to an Alanine (ACA>GCA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Thr2635Ala was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Threonine and Alanine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Thr2635Ala occurs at a position that is not conserved and is within the EB1 binding domain (Azzopardi 2008). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether APC Thr2635Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Ambry Genetics | RCV000575871 | SCV000667381 | likely benign | Hereditary cancer-predisposing syndrome | 2017-07-07 | criteria provided, single submitter | clinical testing | In silico models in agreement (benign);Other strong data supporting benign classification |
| Color | RCV000575871 | SCV000903486 | likely benign | Hereditary cancer-predisposing syndrome | 2016-06-21 | criteria provided, single submitter | clinical testing |