ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1290C>T (p.Gly430=) (rs730881234)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159531 SCV000209491 uncertain significance not provided 2018-09-19 criteria provided, single submitter clinical testing This variant is denoted APC c.1290C>T at the DNA level. It is silent at the coding level, preserving a Glycine at codon 430. In-silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. This variant was not observed at a significant allele frequency in large population cohorts (Lek 2016). Based on currently available evidence, it is unclear whether APC c.1290C>T is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000567240 SCV000667394 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000812968 SCV000953298 uncertain significance Familial adenomatous polyposis 1 2018-08-29 criteria provided, single submitter clinical testing This sequence change affects codon 430 of the APC mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the APC protein. This variant is present in population databases (rs730881234, 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: 181786). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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