Submissions for variant NM_000038.6(APC):c.7955del (p.Ser2652fs)

dbSNP: rs2149996933

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003336453	SCV002133851	pathogenic	Familial adenomatous polyposis 1	2023-11-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser2652Leufs*8) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 192 amino acid(s) of the APC protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with polyposis (Invitae). ClinVar contains an entry for this variant (Variation ID: 1367761). This variant disrupts a region of the APC protein in which other variant(s) (p.Thr2654Argfs*5) have been determined to be pathogenic (PMID: 23159591; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV003336453	SCV004043975	pathogenic	Familial adenomatous polyposis 1	2023-05-16	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.