ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3766C>T (p.Gln1256Ter)

dbSNP: rs77056664
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV001258086 SCV001434928 pathogenic Familial adenomatous polyposis 1 2018-09-27 criteria provided, single submitter clinical testing This c.3766C>T (p.Gln1256*) variant in the APC gene is predicted to introduce a premature translational termination codon. This variant has never been reported in the general population. This variant has been reported in a patient with familial adenomatous polyposis (PMID 10083733) and was also seen in patients in the internal database. Therefore, this c.3766C>T (p.Gln1256*) variant in the APC gene is classified as pathogenic.
Invitae RCV003535794 SCV004292813 pathogenic Familial adenomatous polyposis 1 2023-09-10 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that deletion of this region of the APC protein is causative of disease. 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: 433653). This variant is also known as p.Gln1096X and p.Gln1228*. This premature translational stop signal has been observed in individuals with familial adenomatous polyposis (PMID: 10083733, 19331226, 26446593). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1256*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1588 amino acid(s) of the APC protein.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000502893 SCV000591155 uncertain significance not provided no assertion criteria provided clinical testing

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