ClinVar Miner

Submissions for variant NM_000098.3(CPT2):c.1342T>C (p.Phe448Leu) (rs74315297)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics 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 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 448 of the CPT2 protein (p.Phe448Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs74315297, ExAC 0.02%). This variant has been reported to occur 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). This variant has also been reported in a single affected individual who did not carry the p.Lys414Thrfs*7 truncation but carried the pathogenic p.Ser113Leu variant on the opposite chromosome, which is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease (PMID: 12673791). ClinVar contains an entry for this variant (Variation ID: 8960). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant has been observed in many individuals affected with CPT2-deficiency, but it is typically observed in cis with an upstream truncating variant, and its independent impact on CPT2 protein function is not known. For these reasons, this change has been classified as a Variant of Uncertain Significance.
GeneReviews RCV000202478 SCV000153667 pathogenic Carnitine palmitoyltransferase II deficiency 2014-05-15 no assertion criteria provided literature only

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