Submissions for variant NM_000038.6(APC):c.3184_3200dup (p.Gln1067fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002322772	SCV002609452	pathogenic	Hereditary cancer-predisposing syndrome	2020-11-13	criteria provided, single submitter	clinical testing	The c.3184_3200dup17 pathogenic mutation, located in coding exon 15 of the APC gene, results from a duplication of 17 nucleotides at position 3184, causing a translational frameshift with a predicted alternate stop codon (p.Q1067Hfs*65). This alteration occurs at the 3' terminus of APC gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 1713 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function and a significant portion of the protein is affected. This alteration was identified in an individual with a clinical presentation consistent with familial adenomatous (FAP) (Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc.	RCV004565263	SCV004044119	pathogenic	Familial adenomatous polyposis 1	2023-05-08	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.