ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2834_2835delinsTT (p.Arg945Ile) (rs786204162)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000168163 SCV000218824 uncertain significance Familial adenomatous polyposis 1 2018-10-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with isoleucine at codon 945 of the APC protein (p.Arg945Ile). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and isoleucine. This variant is reported as two separate single-nucleotide changes in population databases (c.2834G>T, ExAC < 0.001% and c.2835G>T, ExAC < 0.001%). However, in the read data for 6/7 individuals displayed in the ExAC browser, these two variants are in cis. This recapitulates the variant observed here (c.2834_2835delGGinsTT) and indicates that this variant is very likely present in the population databases at < 0.001%. This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 188226). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000215714 SCV000274062 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000215714 SCV000681555 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-08 criteria provided, single submitter clinical testing

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