ClinVar Miner

Submissions for variant NM_000110.3(DPYD):c.1679T>G (p.Ile560Ser) (rs55886062)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410952 SCV000486271 likely pathogenic Dihydropyrimidine dehydrogenase deficiency 2016-04-28 criteria provided, single submitter clinical testing
Diasio Lab, Mayo Clinic RCV000086474 SCV000118640 not provided not provided no assertion provided not provided
GeneDx RCV000086474 SCV000321560 pathogenic not provided 2018-10-02 criteria provided, single submitter clinical testing he I560S variant in the DPYD gene was initially reported in the heterozygous state in an individual with reduced dihydropyrimidine dehydrogenase (DPD) activity and 5-fluorouracil (5-FU) toxicity (Collie-Duguid et al., 2000). The I560S variant was subsequently reported in the compound heterozygous state in an individual with profound DPD deficiency and 5-FU toxicity (Johnson et al., 2002). In addition, functional studies have shown that this variant impairs DPD enzyme function, showing a 75% reduction in activity relative to wild type (Offer et al., 2013). The I560S variant is observed in 77/126,112 (0.06%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). The I560S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. The I560S variant is considered a pathogenic variant.
PharmGKB RCV000211360 SCV000268364 drug response capecitabine response - Toxicity/ADR 2018-01-11 reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000211143 SCV000268365 drug response fluorouracil response - Toxicity/ADR 2018-01-11 reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000211265 SCV000268366 drug response Pyrimidine analogues response - Toxicity/ADR 2018-01-11 reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000211391 SCV000268367 drug response tegafur response - Toxicity/ADR 2018-01-11 reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.

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