ClinVar Miner

Submissions for variant NM_000098.3(CPT2):c.1342T>C (p.Phe448Leu)

gnomAD frequency: 0.00021  dbSNP: rs74315297
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000178040 SCV000230026 other not provided 2015-03-02 criteria provided, single submitter clinical testing
GeneDx RCV000430397 SCV000512764 benign not specified 2015-04-08 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000202478 SCV000632585 uncertain significance Carnitine palmitoyltransferase II deficiency 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 448 of the CPT2 protein (p.Phe448Leu). This variant is present in population databases (rs74315297, gnomAD 0.5%). This missense change has been observed in individual(s) with autosomal recessive carnitine palmitoyltransferase II deficiency. It is often reported in cis with the truncating variant c.1239_1240del (p.Lys414Thrfs*7), and this haplotype is a common cause of CPT2-deficiency (PMID: 10090476, 12673791, 12707442, 21913903). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 8960). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CPT2 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Myriad Genetics, Inc. RCV001810398 SCV002060051 uncertain significance Carnitine palmitoyl transferase II deficiency, severe infantile form; Carnitine palmitoyl transferase II deficiency, myopathic form; Carnitine palmitoyl transferase II deficiency, neonatal form 2021-10-27 criteria provided, single submitter clinical testing NM_000098.2(CPT2):c.1342T>C(F448L) is a missense variant classified as a variant of uncertain significance in the context of carnitine palmitoyltransferase II deficiency. F448L has been observed in cases with relevant disease (PMID: 12673791). Functional assessments of this variant are not available in the literature. F448L has been observed in population frequency databases (gnomAD: ASJ 0.49%). In summary, there is insufficient evidence to classify NM_000098.2(CPT2):c.1342T>C(F448L) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
GeneReviews RCV000202478 SCV000153667 uncertain significance Carnitine palmitoyltransferase II deficiency 2017-03-16 no assertion criteria provided literature only
GenomeConnect - Invitae Patient Insights Network RCV000202478 SCV004228578 not provided Carnitine palmitoyltransferase II deficiency no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 06-11-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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