Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002516297 | SCV000282840 | uncertain significance | Familial adenomatous polyposis 1 | 2022-07-08 | 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 236653). 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 glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2735 of the APC protein (p.Gly2735Arg). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001420802 | SCV001623173 | uncertain significance | not specified | 2021-04-16 | criteria provided, single submitter | clinical testing | Variant summary: APC c.8203G>C (p.Gly2735Arg) results in a non-conservative amino acid change located in the Eb-1 binding domain (IPR009232) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251340 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.8203G>C in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002429086 | SCV002679714 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-12-13 | criteria provided, single submitter | clinical testing | The p.G2735R variant (also known as c.8203G>C), located in coding exon 15 of the APC gene, results from a G to C substitution at nucleotide position 8203. The glycine at codon 2735 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 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 70000 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.G2735R remains unclear. |
| Baylor Genetics | RCV002516297 | SCV004198358 | uncertain significance | Familial adenomatous polyposis 1 | 2023-09-17 | criteria provided, single submitter | clinical testing |