ClinVar Miner

Submissions for variant NM_000038.6(APC):c.379A>G (p.Ser127Gly) (rs200089324)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167102 SCV000217932 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Counsyl RCV000410052 SCV000488957 uncertain significance Familial adenomatous polyposis 1 2016-07-25 criteria provided, single submitter clinical testing
GeneDx RCV000034386 SCV000564560 uncertain significance not provided 2018-05-15 criteria provided, single submitter clinical testing This variant is denoted APC c.379A>G at the cDNA level, p.Ser127Gly (S127G) at the protein level, and results in the change of a Serine to a Glycine (AGC>GGC). This variant has been observed in at least two individuals with polyposis (Kohoutova 2002, Kerr 2013). In addition, this variant was observed in 1/572 individuals with atherosclerosis, with no specific information about cancer history (Johnston 2012). APC Ser127Gly was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether APC Ser127Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000410052 SCV000647476 uncertain significance Familial adenomatous polyposis 1 2018-07-29 criteria provided, single submitter clinical testing This sequence change replaces serine with glycine at codon 127 of the APC protein (p.Ser127Gly). The serine residue is highly conserved and there is a small physicochemical difference between serine and glycine. This variant is present in population databases (rs200089324, ExAC 0.004%). This variant has been reported in individuals affected with adenomatous polyposis (PMID: 11933206, 21859464, 23159591). ClinVar contains an entry for this variant (Variation ID: 41504). 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 tolerated, 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.
Color RCV000167102 SCV000911087 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-21 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034386 SCV000043103 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.

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