ClinVar Miner

Submissions for variant NM_000098.3(CPT2):c.1369A>T (p.Lys457Ter) (rs756931329)

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
Counsyl RCV000169067 SCV000220232 likely pathogenic Carnitine palmitoyltransferase II deficiency, infantile 2014-04-08 criteria provided, single submitter literature only
Invitae RCV000689502 SCV000817156 pathogenic Carnitine palmitoyltransferase II deficiency 2020-09-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys457*) in the CPT2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs756931329, ExAC 0.01%). This variant has been reported in an individual affected with carnitine palmitoyltransferase 2 deficiency (PMID: 16996287). ClinVar contains an entry for this variant (Variation ID: 188753). Loss-of-function variants in CPT2 are known to be pathogenic (PMID: 16781677, 16996287). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000762944 SCV000893367 pathogenic Carnitine palmitoyltransferase II deficiency, infantile; Carnitine palmitoyltransferase II deficiency, myopathic, stress-induced; Carnitine palmitoyltransferase II deficiency, lethal neonatal; Encephalopathy, acute, infection-induced, 4, susceptibility to 2018-10-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000689502 SCV001362328 pathogenic Carnitine palmitoyltransferase II deficiency 2021-05-17 criteria provided, single submitter clinical testing Variant summary: CPT2 c.1369A>T (p.Lys457X) 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 3.6e-05 in 251282 control chromosomes (gnomAD). c.1369A>T has been reported in the literature in individuals (in compound heterozygous states) affected with Carnitine Palmitoyltransferase II Deficiency and also rhabdomyolysis (Isackson_2006, Sambuughin_2018, Tangeraas_2020). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (Sambuughin_2018, Tangeraas_2020). Two other ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneDx RCV001567590 SCV001791303 pathogenic not provided 2020-11-24 no assertion criteria provided clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 30094188, 25525159, 16996287)

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.