Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000214175 | SCV000278255 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-09-10 | criteria provided, single submitter | clinical testing | The p.E2753G variant (also known as c.8258A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 8258. The glutamic acid at codon 2753 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 6501 samples (13002 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.003% (greater than 32000 alleles tested) in our clinical cohort. This amino acid position is well 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 p.E2753G remains unclear. |
Invitae | RCV000468899 | SCV000552462 | uncertain significance | Familial adenomatous polyposis 1 | 2016-04-05 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a APC-related disease. This sequence change replaces glutamic acid with glycine at codon 2753 of the APC protein (p.Glu2753Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. |
Counsyl | RCV000468899 | SCV000786033 | uncertain significance | Familial adenomatous polyposis 1 | 2018-02-08 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV003316231 | SCV004019611 | uncertain significance | Familial adenomatous polyposis 1 | 2023-02-15 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |