Submissions for variant NM_000038.6(APC):c.7959_7962del (p.Thr2654fs)

dbSNP: rs1554088793

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000657194	SCV000778918	pathogenic	not provided	2020-05-18	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 23159591)
Invitae	RCV003534544	SCV003439191	likely pathogenic	Familial adenomatous polyposis 1	2023-05-16	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. ClinVar contains an entry for this variant (Variation ID: 545737). This premature translational stop signal has been observed in individual(s) with clinical features of familial adenomatous polyposis (PMID: 23159591; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr2654Argfs*5) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 190 amino acid(s) of the APC protein.