ClinVar Miner

Submissions for variant NM_000038.6(APC):c.268A>G (p.Lys90Glu) (rs763184444)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000528829 SCV000647258 uncertain significance Familial adenomatous polyposis 1 2017-09-05 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 90 of the APC protein (p.Lys90Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs763184444, ExAC 0.001%) but has not been reported in the literature in individuals with an APC-related disease. ClinVar contains an entry for this variant (Variation ID: 217952). 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, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000580141 SCV000681547 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000201975 SCV000918465 uncertain significance not specified 2017-12-11 criteria provided, single submitter clinical testing Variant summary: The c.268A>G (p.Lys90Glu) in APC gene is a missense variant involves a highly conserved nucleotide located outside of any known functional domain or repeat. The 3/5 in silico tools predict deleterious outcome for this variant, however no functional studies supporting these predictions were published at the time of evaluation. The c.268A>G was identified in the control population dataset of gnomAD at a low frequency of 0.000012 (3/ 246244 chrs tested). The observed frequency does not exceed the maximum expected allele frequency for a pathogenic variant of 0.00007, suggesting that it is not a common polymorphism. The variant has been identified together with APC c.677delA in an individual undergoing genetic testing due to family history of FAP. To our knowledge, the variant has not been reported in affected individuals via peer-reviewed reports, but is cited as VUS by a reputable database/clinical laboratory. Taken together, the variant was classified as VUS, until new information becomes available.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000201975 SCV000256952 uncertain significance not specified no assertion criteria provided research

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