ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3775A>T (p.Ile1259Leu) (rs762391822)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000590453 SCV000694037 uncertain significance not provided 2016-05-09 criteria provided, single submitter clinical testing Variant summary: The APC c.3775A>T (p.Ile1259Leu) variant involves the alteration of a conserved nucleotide, resulting in a missense change at Ile1259 to Leu. Ile1259 lies in the DNA repair inhibitory domain; this domain is involved in the regulation of the base excision repair (BER) pathway. APC blocks Pol--directed BER by blocking the dRP-lyase and strand-displacement activities of Pol- (PMID:26334567). Using site-directed mutagenesis, the APC amino acid residues Ile1259 and Tyr1262 have been shown to be important for the interaction and functional activity of Pol-. However, this particular missense change, Ile1259Leu was not studied (I1259A was examined; PMID:17176113). 3/4 in silico tools predict a benign outcome (SNPs&GO not captured due to low reliability index). However, this variant has not been evaluated for functional impact by in vivo/vitro studies.This variant was absent in 120528 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.

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