ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3305A>G (p.Tyr1102Cys) (rs769608546)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481373 SCV000569787 uncertain significance not provided 2018-11-12 criteria provided, single submitter clinical testing This variant is denoted APC c.3305A>G at the cDNA level, p.Tyr1102Cys (Y1102C) at the protein level, and results in the change of a Tyrosine to a Cysteine (TAC>TGC). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. APC APC Tyr1102Cys was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the 15-amino acid repeat Beta-catenin binding domain (Azzopardi 2008). 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 Tyr1102Cys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000824516 SCV000965416 uncertain significance Familial adenomatous polyposis 1 2018-10-24 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 1102 of the APC protein (p.Tyr1102Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs769608546, ExAC 0.01%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 420808). 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: "Possibly 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.

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