ClinVar Miner

Submissions for variant NM_000098.3(CPT2):c.370C>T (p.Arg124Ter) (rs201065226)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000185829 SCV000238778 pathogenic not provided 2018-11-06 criteria provided, single submitter clinical testing The R124X nonsense pathogenic variant in the CPT2 gene has been reported previously in association with carnitine palmitoyltransferase II (CPT2) deficiency (Yang et al., 1998). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is found in CPT2 panel(s).
Counsyl RCV000411770 SCV000487388 likely pathogenic Carnitine palmitoyltransferase II deficiency, myopathic, stress-induced 2015-12-21 criteria provided, single submitter clinical testing
Counsyl RCV000410924 SCV000487390 likely pathogenic Carnitine palmitoyltransferase II deficiency, lethal neonatal 2015-12-21 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000185829 SCV000610687 pathogenic not provided 2017-10-02 criteria provided, single submitter clinical testing
Invitae RCV000707179 SCV000836264 pathogenic Carnitine palmitoyltransferase II deficiency 2020-09-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg124*) in the CPT2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with carnitine palmitoyltransferase II deficiency (PMID: 9562964, 16996287, 22652984). ClinVar contains an entry for this variant (Variation ID: 203659). Loss-of-function variants in CPT2 are known to be pathogenic (PMID: 16781677, 16996287). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV001004158 SCV001162924 pathogenic Carnitine palmitoyltransferase II deficiency, infantile; Carnitine palmitoyltransferase II deficiency, lethal neonatal criteria provided, single submitter clinical testing
Myriad Women's Health, Inc. RCV000409811 SCV001194168 pathogenic Carnitine palmitoyltransferase II deficiency, infantile 2019-12-11 criteria provided, single submitter clinical testing NM_000098.2(CPT2):c.370C>T(R124*) is classified as pathogenic in the context of carnitine palmitoyltransferase II deficiency. Sources cited for classification include the following: PMID 16996287, 23322164 and 9562964. Classification of NM_000098.2(CPT2):c.370C>T(R124*) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000707179 SCV001478655 pathogenic Carnitine palmitoyltransferase II deficiency 2021-01-29 criteria provided, single submitter clinical testing Variant summary: CPT2 c.370C>T (p.Arg124X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251336 control chromosomes (gnomAD). c.370C>T has been reported in the literature in compound heterozygous individuals affected with adult-onset Carnitine Palmitoyltransferase II Deficiency (Yang_1998, Isackson_2006), while it has also been reported in a homozygous individual with lethal neonatal form of the disease (McGill_2012). These data indicate that the variant is likely to be associated with disease. Six ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc. RCV000707179 SCV001461216 pathogenic Carnitine palmitoyltransferase II deficiency 2020-09-16 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000185829 SCV001743561 pathogenic not provided no assertion criteria provided clinical testing

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