ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1956C>T (p.His652=) (rs1064793716)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482661 SCV000566856 likely pathogenic not provided 2018-04-09 criteria provided, single submitter clinical testing This variant is denoted APC c.1956C>T at the DNA level. Although the variant is a synonymous substitution at the coding level, preserving a Histidine at codon 652, it has been demonstrated to cause exon skipping by RNA analysis (Aretz 2004, Schwarzová 2013). APC c.1956C>T was not observed in large population cohorts (Lek 2016).This variant has been observed in individuals with classic and attenuated familial adenomatous polyposis and has shown segregation with disease in internal cases, in the literature, and by another clinical laboratory (Aretz 2004, Friedl 2005, Schwarzová 2013, SCV000647207.1). Based on currently available evidence, we consider APC c.1956C>T to be a likely pathogenic variant.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000502897 SCV000591098 pathogenic Familial adenomatous polyposis criteria provided, single submitter clinical testing
Invitae RCV000535440 SCV000647207 likely pathogenic Familial adenomatous polyposis 1 2017-07-11 criteria provided, single submitter clinical testing This sequence change affects codon 652 of the APC mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with typical or attenuated familial adenomatous polyposis (FAP) (PMID: 15459959, 22987206). This variant has been also observed in a family affected with FAP (Invitae). ClinVar contains an entry for this variant (Variation ID: 419202). Experimental studies have shown that this variant causes skipping of exon 14 (exon 15 if using systematic exon numbering) in blood as well as other tissue types from affected individuals (PMID: 15459959, 22987206). 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.
Ambry Genetics RCV001013836 SCV001174471 likely pathogenic Hereditary cancer-predisposing syndrome 2019-08-12 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Functionally-validated splicing mutation;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Rarity in general population databases (dbsnp, esp, 1000 genomes)

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