Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000567141 | SCV000667666 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-10-21 | criteria provided, single submitter | clinical testing | The p.E601G variant (also known as c.1802A>G), located in coding exon 14 of the APC gene, results from an A to G substitution at nucleotide position 1802. The glutamic acid at codon 601 is replaced by glycine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6502 samples (13004 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 90000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. 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. |
| Sema4, |
RCV000567141 | SCV002530364 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-27 | criteria provided, single submitter | curation | |
| Invitae | RCV003744554 | SCV002590944 | uncertain significance | Familial adenomatous polyposis 1 | 2022-08-22 | criteria provided, single submitter | clinical testing | 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. 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). ClinVar contains an entry for this variant (Variation ID: 482421). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 601 of the APC protein (p.Glu601Gly). |