Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000129231 | SCV000183986 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-02-10 | criteria provided, single submitter | clinical testing | The p.R805G variant (also known as c.2413C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 2413. The arginine at codon 805 is replaced by glycine, an amino acid with dissimilar properties. This variant has not been detected in conjunction with a pathogenic mutation to date. 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 completely conserved through reptiles on sequence alignment. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.R805G remains unclear. |
Invitae | RCV002514714 | SCV000552600 | uncertain significance | Familial adenomatous polyposis 1 | 2021-12-07 | 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 140951). 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 arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 805 of the APC protein (p.Arg805Gly). |