ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3080A>G (p.Tyr1027Cys)

dbSNP: rs869312784
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
University of Washington Department of Laboratory Medicine, University of Washington RCV000210203 SCV000266140 uncertain significance Colorectal cancer, susceptibility to 2015-11-20 criteria provided, single submitter clinical testing
Invitae RCV003743640 SCV000647421 uncertain significance Familial adenomatous polyposis 1 2023-12-02 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1027 of the APC protein (p.Tyr1027Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with a personal history of colon polyps and a family history of colon and breast cancer (PMID: 26845104). ClinVar contains an entry for this variant (Variation ID: 224553). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV000562346 SCV000672594 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-22 criteria provided, single submitter clinical testing The p.Y1027C variant (also known as c.3080A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 3080. The tyrosine at codon 1027 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000562346 SCV001347726 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-11 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with cysteine at codon 1027 of the APC protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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