Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000223252 | SCV000274439 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-03-04 | criteria provided, single submitter | clinical testing | The p.G1702R variant (also known as c.5104G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 5104. The glycine at codon 1702 is replaced by arginine, an amino acid with dissimilar 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 0.005% (greater than 21000 alleles tested) in our clinical cohort. This amino acid position is poorly conserved in available vertebrate species, with arginine being the common amino acid in the majority of 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.G1702R remains unclear. |
Gene |
RCV000236162 | SCV000292713 | uncertain significance | not provided | 2015-11-03 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.5104G>A at the cDNA level, p.Gly1702Arg (G1702R) at the protein level, and results in the change of a Glycine to an Arginine (GGA>AGA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Gly1702Arg 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 Glycine and Arginine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Gly1702Arg occurs at a position that is not conserved and is located within the 20-aa beta-catenin down-regulating, SAMP repeats and axin binding domains (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 Gly1702Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Color Diagnostics, |
RCV000223252 | SCV001341621 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-25 | criteria provided, single submitter | clinical testing |