Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000166644 | SCV000217448 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-11-03 | criteria provided, single submitter | clinical testing | The p.G2227V variant (also known as c.6680G>T), located in coding exon 15 of the APC gene, results from a G to T substitution at nucleotide position 6680. The glycine at codon 2227 is replaced by valine, 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 6499 samples (12998 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 13000 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 probably damaging and tolerated by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.G2227V remains unclear. |
| Labcorp Genetics |
RCV000228117 | SCV002188618 | uncertain significance | Familial adenomatous polyposis 1 | 2022-07-12 | 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: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 186972). This missense change has been observed in individual(s) with clinical features of APC-related conditions (PMID: 24599579). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2227 of the APC protein (p.Gly2227Val). |
| Baylor Genetics | RCV000228117 | SCV004204152 | uncertain significance | Familial adenomatous polyposis 1 | 2023-05-06 | criteria provided, single submitter | clinical testing |