Submissions for variant NM_000038.6(APC):c.298del (p.Glu100fs)

dbSNP: rs1064794224

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486524	SCV000568263	likely pathogenic	not provided	2016-10-03	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in APC is denoted c.298delG at the cDNA level and p.Glu100LysfsX25 (E100KfsX25) at the protein level. The normal sequence, with the base that is deleted in brackets, is CCGG[delG]AAGG. The deletion causes a frameshift which changes a Glutamic Acid to a Lysine at codon 100, and creates a premature stop codon at position 25 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. APC c.298delG has been identified in a patient with fundic gland polyposis and a family history of colon cancer and polyps (Ohtaka 2011). Based on the currently available information, we consider this deletion to be a likely pathogenic variant.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000486524	SCV000600071	likely pathogenic	not provided	2017-05-05	criteria provided, single submitter	clinical testing
Invitae	RCV002230916	SCV000768278	pathogenic	Familial adenomatous polyposis 1	2023-10-23	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu100Lysfs*25) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 21646762). ClinVar contains an entry for this variant (Variation ID: 419991). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV002230916	SCV004044238	pathogenic	Familial adenomatous polyposis 1	2023-04-25	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Baylor Genetics	RCV002525821	SCV004200441	pathogenic	Familial adenomatous polyposis 1	2021-08-12	criteria provided, single submitter	clinical testing
GenomeConnect, ClinGen	RCV002230916	SCV002075247	not provided	Familial adenomatous polyposis 1		no assertion provided	phenotyping only	Variant classified as Likely pathogenic and reported on 10-03-2016 by Lab or GTR ID 507401. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.