ClinVar Miner

Submissions for variant NM_000038.5(APC):c.2444A>C (p.Asn815Thr) (rs762990578)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000563002 SCV000667316 likely benign Hereditary cancer-predisposing syndrome 2017-01-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Color RCV000563002 SCV000910971 likely benign Hereditary cancer-predisposing syndrome 2016-07-20 criteria provided, single submitter clinical testing
Counsyl RCV000197360 SCV000488943 uncertain significance Familial adenomatous polyposis 1 2016-07-26 criteria provided, single submitter clinical testing
GeneDx RCV000493690 SCV000581705 not provided not provided no assertion provided clinical testing This variant is denoted APC c.2444A>C at the cDNA level, p.Asn815Thr (N815T) at the protein level, and results in the change of an Asparagine to a Threonine (AAT>ACT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Asn815Thr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a conservative substitution of one neutral polar amino acid for another, altering a position that is well conserved throughout mammals and is located within a serine-rich region (UniProt). In silico analyses are inconsistent with regard to the effect this variant may have on protein structure and function. Based on the currently available information, we consider APC Asn815Thr to be a variant of uncertain significance.
Invitae RCV000197360 SCV000254000 uncertain significance Familial adenomatous polyposis 1 2018-06-11 criteria provided, single submitter clinical testing This sequence change replaces asparagine with threonine at codon 815 of the APC protein (p.Asn815Thr). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and threonine. This variant is present in population databases (rs762990578, ExAC 0.003%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 216156). 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.
PreventionGenetics RCV000493690 SCV000805381 uncertain significance not provided 2017-10-16 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000563002 SCV000805206 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-15 no assertion criteria provided clinical testing

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