ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6779G>A (p.Ser2260Asn) (rs587781393)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129236 SCV000183993 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000204391 SCV000260672 uncertain significance Familial adenomatous polyposis 1 2018-08-27 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 2260 of the APC protein (p.Ser2260Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. This variant is present in population databases (rs587781393, ExAC 0.002%). This variant has not been reported in the literature in individuals with a APC-related disease. ClinVar contains an entry for this variant (Variation ID: 140955). Algorithms developed to predict the effect of missense changes on protein structure and function 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.
GeneDx RCV000479990 SCV000572068 uncertain significance not provided 2018-08-08 criteria provided, single submitter clinical testing This variant is denoted APC c.6779G>A at the cDNA level, p.Ser2260Asn (S2260N) at the protein level, and results in the change of a Serine to an Asparagine (AGC>AAC). This variant was reported in an individual with a personal history of breast cancer and family history of breast and gastric cancer (Lovejoy 2018). APC Ser2260Asn was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the basic 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 Ser2260Asn is pathogenic or benign. We consider it to be a variant of uncertain significance.
Color RCV000129236 SCV000687094 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-24 criteria provided, single submitter clinical testing

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