Submissions for variant NM_000038.6(APC):c.249del (p.Gly84fs)

dbSNP: rs878853428

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV004563228	SCV000282719	pathogenic	Familial adenomatous polyposis 1	2022-09-07	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 236575). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly84Glufs*2) 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).
GeneDx	RCV000657492	SCV000779227	pathogenic	not provided	2018-03-21	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in APC is denoted c.249delT at the cDNA level and p.Gly84GlufsX2 (G84EfsX2) at the protein level. The normal sequence, with the base that is deleted in brackets, is TCCC[delT]GGAG. The deletion causes a frameshift which changes a Glycine to a Glutamic Acid at codon 84, and creates a premature stop codon at position 2 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Myriad Genetics, Inc.	RCV004563228	SCV004045245	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.