ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4311A>G (p.Lys1437=) (rs371784771)

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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 RCV000166619 SCV000217423 likely benign Hereditary cancer-predisposing syndrome 2014-10-28 criteria provided, single submitter clinical testing
GeneDx RCV000236282 SCV000292459 uncertain significance not specified 2016-01-04 criteria provided, single submitter clinical testing This variant is denoted APC c.4311A>G at the DNA level. Although this variant is silent at the coding level, preserving a Lysine at codon 1437, it is predicted to create a strong cryptic splice donor site far upstream. 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 pathogenic or benign. APC c.4311A>G was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. The nucleotide which is altered, an adenine (A) at base 4311, is not conserved. Based on currently available information, it is unclear whether APC c.4311A>G is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000457831 SCV000552764 uncertain significance Familial adenomatous polyposis 1 2018-10-31 criteria provided, single submitter clinical testing This sequence change affects codon 1437 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 not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an APC-related disease. ClinVar contains an entry for this variant (Variation ID: 186951). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare silent change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance.
Counsyl RCV000457831 SCV000785393 likely benign Familial adenomatous polyposis 1 2017-08-04 criteria provided, single submitter clinical testing
Color RCV000166619 SCV000911737 likely benign Hereditary cancer-predisposing syndrome 2016-10-31 criteria provided, single submitter clinical testing

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