ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2805C>A (p.Tyr935Ter) (rs137854575)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000844610 SCV000058709 pathogenic Familial multiple polyposis syndrome 2014-01-27 criteria provided, single submitter clinical testing The Tyr935X variant in APC has been reported in >20 individuals with FAP, segreg ated with disease in at least 12 affected family members (see references), and w as absent from large population studies (rs137854575). This nonsense variant le ads to a premature termination codon at position 935, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the APC gene is an established disease mechanism in individuals with FAP. In summary, this v ariant meets our criteria to be classified as pathogenic (http://pcpgm.partners. org/LMM) based upon segregation studies and absence from controls.
Ambry Genetics RCV000129305 SCV000184067 pathogenic Hereditary cancer-predisposing syndrome 2017-11-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000202012 SCV000209507 pathogenic not provided 2018-06-07 criteria provided, single submitter clinical testing This pathogenic variant is denoted APC c.2805C>A at the cDNA level and p.Tyr935Ter (Y935X) at the protein level. The substitution creates a nonsense variant, changing a Tyrosine to a premature stop codon (TAC>TAA). This variant is predicted to cause loss of normal protein function through protein truncation. APC Tyr935Ter has been reported in association with Familial Adenomatous Polyposis (FAP) and is considered pathogenic (Fodde 1992, Won 1999, Aceto 2005, Kim 2005, Agatea 2015, Simbolo 2015, Khan 2017).
University of Washington Department of Laboratory Medicine,University of Washington RCV000210151 SCV000266007 pathogenic Colorectal cancer, susceptibility to 2015-11-20 criteria provided, single submitter clinical testing
Invitae RCV000000848 SCV000552450 pathogenic Familial adenomatous polyposis 1 2018-05-13 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the last exon of the APC mRNA at codon 935 (p.Tyr935*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 1909 amino acids of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with familial adenomatous polyposis (FAP) (PMID: 1324223, 20924072, 11933206, 10094547, 11748858, 17411426, 16088911, 20685668, 26300997, 16317745, 10083733, 1944466, 12173026, 8381579, 10713886, 15024739, 8990002, 15108288), and individuals affected with FAP and thyroid cancer (PMID: 19793053, 10713886). ClinVar contains an entry for this variant (Variation ID: 810). 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 RCV000502795 SCV000591118 pathogenic Familial adenomatous polyposis 2014-10-31 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000202012 SCV000600067 pathogenic not provided 2015-11-04 criteria provided, single submitter clinical testing
Color RCV000129305 SCV000686914 pathogenic Hereditary cancer-predisposing syndrome 2017-08-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763542 SCV000894355 pathogenic Desmoid disease, hereditary; Carcinoma of colon; Familial adenomatous polyposis 1; Neoplasm of stomach; Hepatocellular carcinoma 2018-10-31 criteria provided, single submitter clinical testing
OMIM RCV000000848 SCV000020998 pathogenic Familial adenomatous polyposis 1 1992-08-01 no assertion criteria provided literature only
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202012 SCV000256955 pathogenic not provided no assertion criteria provided research

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