Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003650449 | SCV000253731 | pathogenic | Familial adenomatous polyposis 1 | 2016-05-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Truncating variants in APC are known to be pathogenic. This particular truncation has been previously reported in three families affected with Familial Adenomatous Polyposis (PMID: 14729851, 19029688, 26163615). This sequence change deletes 4 nucleotides in exon 16 of the APC mRNA (c.3921_3924delAAAA), causing a frameshift at codon 1307. This creates a premature translational stop signal in the last exon of the APC mRNA (p.Ile1307Metfs*13). While this is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated APC protein. |
| Ambry Genetics | RCV002372182 | SCV002624905 | pathogenic | Hereditary cancer-predisposing syndrome | 2014-12-01 | criteria provided, single submitter | clinical testing | The c.3921_3924delAAAA pathogenic mutation, located in coding exon 15 of the APC gene, results from a deletion of 4 nucleotides between nucleotide positions 3921 and 3924, causing a translational frameshift with a predicted alternate stop codon. This pathogenic mutation has been reported in two children from one Polish family who were diagnosed with FAP at ages 8 years and 4 years (Plawski A et al. J Med Genet. 2004 Jan;41(1):e11). In addition to the clinical data presented in the literature, since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |
| Myriad Genetics, |
RCV003335192 | SCV004045033 | pathogenic | Familial adenomatous polyposis 1 | 2023-05-09 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477664 | SCV004219317 | likely pathogenic | not provided | 2023-09-12 | criteria provided, single submitter | clinical testing | This frameshift variant creates a premature stop codon in the last exon of the APC gene. While this is not expected to trigger nonsense-mediated decay of the affected allele, the resulting disruption of approximately 54% of the coding sequences of the APC gene is predicted to significantly impact protein function. In the published literature, this variant has been reported in individuals and families with FAP (PMIDs: 26163615 (2015), 19029688 (2008), 14729851 (2004)). A similar truncating variant, c.3920_3923del (p.Ile1307Lysfs*13, also known as 3938del4) has also been described as deleterious in a family with FAP (PMID: 9341879 (1997)). The c.3921_3924del (p.Ile1307Metfs*13) variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as likely pathogenic. |