ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3202_3205del (p.Ser1068fs) (rs587779353)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130649 SCV000185529 pathogenic Hereditary cancer-predisposing syndrome 2017-02-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000206027 SCV000260417 pathogenic Familial adenomatous polyposis 1 2018-12-14 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the APC gene (p.Ser1068Glyfs*57). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1776 amino acids of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals and families affected with familial adenomatous polyposis (FAP) (PMID: 8395941, 10646887, 19725996, 20333795, 23159591), with evidence of segregation with disease (PMID: 8395941, 10646887). This variant is also known as 3202delTCAA or 3199_3202delCAAT in the literature. ClinVar contains an entry for this variant (Variation ID: 88914). Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). For these reasons, this variant has been classified as Pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000501023 SCV000591134 pathogenic Familial adenomatous polyposis criteria provided, single submitter clinical testing
GeneDx RCV000201995 SCV000778914 pathogenic not provided 2017-06-22 criteria provided, single submitter clinical testing This deletion of four nucleotides in APC is denoted c.3202_3205delTCAA at the cDNA level and p.Ser1068GlyfsX57 (S1068GfsX57) at the protein level. The normal sequence, with the bases that are deleted in brackets, is ACAA[delTCAA]GGAA. The deletion causes a frameshift which changes a Serine to a Glycine at codon 1068, and creates a premature stop codon at position 57 of the new reading frame. This variant is predicted to cause loss of normal protein function through protein truncation. APC Ser1068GlyfsX57 has been observed in many families with attenuated or classic familial adenomatous polyposis (AFAP/FAP) (Paul 1993, Wallis 1999, Enomoto 2000, De Rosa 2003, Friedl 2005, Kanter-Smoler 2008, Plawski 2008, Andresen 2009, Lagarde 2010, Rivera 2011, Kerr 2013). Additionally, this variant has been observed in at least two unrelated children with a personal history of hepatoblastoma (Aretz 2006), as well as in individuals with osteomas, epidermoid cysts, duodenal/gastric adenomas, and/or congenital hypertrophy of the retinal pigment epithelium (CHRPE) (Paul 1993, Enomoto 2000, Kerr 2013). We consider this variant to be pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000201995 SCV000256969 pathogenic not provided no assertion criteria provided clinical testing

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