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

gnomAD frequency: 0.00001  dbSNP: rs201065226

Total submissions: 14

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 palmitoyl transferase II deficiency, myopathic form	2015-12-21	criteria provided, single submitter	clinical testing
Counsyl	RCV000410924	SCV000487390	likely pathogenic	Carnitine palmitoyl transferase II deficiency, neonatal form	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
Labcorp Genetics (formerly Invitae), Labcorp	RCV000707179	SCV000836264	pathogenic	Carnitine palmitoyltransferase II deficiency	2023-09-15	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 203659). 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. Loss-of-function variants in CPT2 are known to be pathogenic (PMID: 16781677, 16996287). This variant is present in population databases (rs201065226, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with carnitine palmitoyltransferase II deficiency (PMID: 9562964, 16996287, 22652984). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV001004158	SCV001162924	pathogenic	Carnitine palmitoyl transferase II deficiency, severe infantile form; Carnitine palmitoyl transferase II deficiency, neonatal form		criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000409811	SCV001194168	pathogenic	Carnitine palmitoyl transferase II deficiency, severe infantile form	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.
Fulgent Genetics, Fulgent Genetics	RCV002500569	SCV002811122	pathogenic	Carnitine palmitoyl transferase II deficiency, severe infantile form; Carnitine palmitoyl transferase II deficiency, myopathic form; Carnitine palmitoyl transferase II deficiency, neonatal form; Encephalopathy, acute, infection-induced, susceptibility to, 4	2021-11-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000409811	SCV004179308	likely pathogenic	Carnitine palmitoyl transferase II deficiency, severe infantile form	2023-04-11	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003474939	SCV004211029	pathogenic	Encephalopathy, acute, infection-induced, susceptibility to, 4	2024-02-14	criteria provided, single submitter	clinical testing
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
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000185829	SCV001952140	pathogenic	not provided		no assertion criteria provided	clinical testing