ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3935G>C (p.Gly1312Ala) (rs587779791)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115088 SCV000148997 uncertain significance not provided 2018-11-01 criteria provided, single submitter clinical testing This variant is denoted APC c.3935G>C at the cDNA level, p.Gly1312Ala (G1312A) at the protein level, and results in the change of a Glycine to an Alanine (GGA>GCA) in exon 16. This variant has not, to our knowledge, been published in the literature as either a mutation or a benign polymorphism. APC Gly1312Ala was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Variant Server, indicating it is not a common benign variant in these populations. This variant is a conservative substitution of one neutral non-polar amino acid for another, altering a position that is only moderately conserved throughout evolution and is located in a domain responsible for down-regulation of APC gene. In silico analyses predict this variant to have a benign effect on protein structure and function. Based on the currently available information, we consider APC Gly1312Ala to be a variant of unknown significance. The variant is found in COLO-HEREDIC panel(s).
Ambry Genetics RCV000562223 SCV000667416 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)
Color RCV000562223 SCV000686958 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-07 criteria provided, single submitter clinical testing
Invitae RCV000646312 SCV000768080 uncertain significance Familial adenomatous polyposis 1 2018-10-11 criteria provided, single submitter clinical testing This sequence change replaces glycine with alanine at codon 1312 of the APC protein (p.Gly1312Ala). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and alanine. This variant is present in population databases (rs587779791, ExAC 0.03%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 127291). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.

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