ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5216A>G (p.Lys1739Arg) (rs769558291)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163875 SCV000214462 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000205541 SCV000260634 uncertain significance Familial adenomatous polyposis 1 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 1739 of the APC protein (p.Lys1739Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs769558291, 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: 184596). 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: "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.
Counsyl RCV000205541 SCV000489173 uncertain significance Familial adenomatous polyposis 1 2016-09-07 criteria provided, single submitter clinical testing
Color RCV000163875 SCV000681715 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589784 SCV000694071 uncertain significance not provided 2016-08-08 criteria provided, single submitter clinical testing Variant summary: The c.5216A>G (p.Lys1739Arg) in APC gene is a missense change that involves a mildly conserved nucleotide and 3/5 in silico tools predict damaging outcome. The variant of interest is located outside of any known functional domain. The variant is present in control dataset of ExAC at a low frequency of 0.000008 (1/ 120650 chrs tested) which does not exceed the estimated maximum allele frequency for a pathogenic allele in this gene (0.00007). This variant has not, to our knowledge, been reported in affected individuals via published reports but is cited as VUS by reputable databases/clinical laboratories. Taking together, the variant was classified as VUS.

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