ClinVar Miner

Submissions for variant NM_000098.3(CPT2):c.886C>T (p.Arg296Ter) (rs727503887)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000153105 SCV000202562 pathogenic not provided 2013-12-27 criteria provided, single submitter clinical testing
Counsyl RCV000169096 SCV000220284 likely pathogenic Carnitine palmitoyltransferase II deficiency, infantile 2014-04-30 criteria provided, single submitter literature only
Invitae RCV000539401 SCV000632615 pathogenic Carnitine palmitoyltransferase II deficiency 2017-04-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 296 (p.Arg296*) of the CPT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CPT2 are known to be pathogenic. This particular variant has been reported in the literature in an individual affected with CPT2 deficiency (PMID: 14605500). This variant is also known as c.906C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 166953). Experimental studies have shown that this change causes reduced fatty acid oxidation and CPT2 activity reduction to 14% of controls in cultured fibroblasts from an individual with this variant (PMID: 14615409). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000539401 SCV000919251 likely pathogenic Carnitine palmitoyltransferase II deficiency 2018-11-29 criteria provided, single submitter clinical testing Variant summary: CPT2 c.886C>T (p.Arg296X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2.5e-05 in 277068 control chromosomes (gnomAD). c.886C>T has been reported in the literature in individuals affected with Carnitine Palmitoyltransferase II Deficiency (Olpin_2003, Tan_2016). One of these patients had a reported CPT II activity of 14% (Olpin_2003). A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
GeneDx RCV000153105 SCV001167707 pathogenic not provided 2019-02-22 criteria provided, single submitter clinical testing The R296X nonsense variant in the CPT2 gene has been reported previously in association with carnitine palmitoyltransferase II deficiency (Olpin et al., 2003; Tan et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R296X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). In summary, we interpret R296X to be a pathogenic variant.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.