ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3535T>A (p.Tyr1179Asn) (rs751249843)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000474534 SCV000552663 uncertain significance Familial adenomatous polyposis 1 2018-12-06 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with asparagine at codon 1179 of the APC protein (p.Tyr1179Asn). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and asparagine. This variant is present in population databases (rs751249843, ExAC 0.002%). This variant has been observed in an individual affected with clinical features of Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 411482). 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: "Tolerated"; 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 RCV000486050 SCV000572396 uncertain significance not provided 2017-10-24 criteria provided, single submitter clinical testing This variant is denoted APC c.3535T>A at the cDNA level, p.Tyr1179Asn (Y1179N) at the protein level, and results in the change of a Tyrosine to an Asparagine (TAT>AAT). This variant has been observed in at least one individual with a Lynch syndrome-associated tumor and/or polyps (Yurgelun 2015). APC Tyr1179Asn was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Tyrosine and Asparagine differ in some properties, this is considered a semi-conservative amino acid substitution. APC Tyr1179Asn occurs at a position that is conserved across species and is not located in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether APC Tyr1179Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000562153 SCV000672511 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000562153 SCV000686941 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-17 criteria provided, single submitter clinical testing

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