Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000567190 | SCV000672535 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-01-07 | criteria provided, single submitter | clinical testing | The c.685_686insCGGACATAC variant (also known as p.I228_L229insPDI), located in coding exon 6 of the APC gene, results from an in-frame CGGACATAC insertion between nucleotide positions 685 and 686. This results in the insertion of an extra three residues (P,D,I) between codons 228 and 229. 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. Since supporting evidence is limited at this time, the clinical significance of c.685_686insCGGACATAC remains unclear. |
| Color Diagnostics, |
RCV000567190 | SCV002053700 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-16 | criteria provided, single submitter | clinical testing | This variant causes an insertion of three amino acids in the APC protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV005091414 | SCV005746289 | uncertain significance | Familial adenomatous polyposis 1 | 2024-12-12 | criteria provided, single submitter | clinical testing | This variant, c.685_686insCGGACATAC, results in the insertion of 3 amino acid(s) of the APC protein (p.Ile228_Leu229insProAspIle), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 485109). 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. |