ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1073A>G (p.Gln358Arg) (rs1064793508)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481456 SCV000566292 uncertain significance not provided 2015-04-16 criteria provided, single submitter clinical testing This variant is denoted APC c.1073A>G at the cDNA level, p.Gln358Arg (Q358R) at the protein level, and results in the change of a Glutamine to an Arginine (CAG>CGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Gln358Arg 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. Since Glutamine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. APC Gln358Arg occurs at a position that is conserved across species and is not located within a known functional domain (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether APC Gln358Arg is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000809558 SCV000949712 uncertain significance Familial adenomatous polyposis 1 2018-08-09 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 358 of the APC protein (p.Gln358Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 418898). 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.

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