ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3535T>C (p.Tyr1179His) (rs751249843)

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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 RCV000167162 SCV000217995 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000203705 SCV000261290 uncertain significance Familial adenomatous polyposis 1 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with histidine at codon 1179 of the APC protein (p.Tyr1179His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 187434). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000235383 SCV000293822 uncertain significance not provided 2018-05-14 criteria provided, single submitter clinical testing This variant is denoted APC c.3535T>C at the cDNA level, p.Tyr1179His (Y1179H) at the protein level, and results in the change of a Tyrosine to a Histidine (TAT>CAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Tyr1179His was not observed at a significant allele frequency in large population cohorts (Lek 2016). APC Tyr1179His is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether APC Tyr1179His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000167162 SCV000686942 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-10 criteria provided, single submitter clinical testing
Counsyl RCV000203705 SCV000784951 uncertain significance Familial adenomatous polyposis 1 2017-02-16 criteria provided, single submitter clinical testing

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