ClinVar Miner

Submissions for variant NM_000098.3(CPT2):c.1148T>A (p.Phe383Tyr) (rs74315295)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000009518 SCV000487431 likely pathogenic Carnitine palmitoyltransferase II deficiency, myopathic, stress-induced 2015-11-30 criteria provided, single submitter clinical testing
Counsyl RCV000009517 SCV000487432 likely pathogenic Carnitine palmitoyltransferase II deficiency, infantile 2015-11-30 criteria provided, single submitter clinical testing
Counsyl RCV000411002 SCV000487433 likely pathogenic Carnitine palmitoyltransferase II deficiency, lethal neonatal 2015-11-30 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762943 SCV000893366 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
Illumina Clinical Services Laboratory,Illumina RCV000202462 SCV000915423 pathogenic Carnitine palmitoyltransferase II deficiency 2018-08-09 criteria provided, single submitter clinical testing Across a selection of the available literature, the CPT2 c.1148T>A (p.Phe383Tyr) missense variant has been reported in a total of nine individuals with carnitine palmitoyltransferase II (CPT II) deficiency, including in seven with the infantile-onset hepatocardiomuscular form and in two with adult-onset myopathic form (Yamamoto et al. 1998; Wataya et al. 1998; Yasuno et al. 2008). Of those presenting with the hepatocardiomuscular form, one was homozygous for the p.Phe383Tyr variant, three, including two siblings, were compound heterozygous for the variant and a second missense variant, and three were heterozygous with no second variant identified. Of those presenting with the myopathic form, one was homozygous for the p.Phe383Tyr variant and one was heterozygous with no second variant identified. The p.Phe383Tyr variant was also detected in a heterozygous state in three healthy parents of individuals with CPT II. The p.Phe383Tyr variant was absent from 80 Japanese controls and is reported at a frequency of 0.00035 in the East Asian population of the Exome Aggregation Consortium. Transient expression of the p.Phe383Tyr variant in COS-1 cells revealed an intermediate level of CPT II enzyme activity at approximately 34% of normal, while very low activity was detected, approximately 10% of normal, when the variant was co-expressed with a second missense variant (Wataya et al. 1998). Based on the collective evidence, the p.Phe383Tyr variant is classified as pathogenic for carnitine palmitoyltransferase II deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000202462 SCV000949879 pathogenic Carnitine palmitoyltransferase II deficiency 2019-10-16 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with tyrosine at codon 383 of the CPT2 protein (p.Phe383Tyr). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and tyrosine. This variant is present in population databases (rs74315295, ExAC 0.03%). This variant has been observed to segregate with CPT2 deficiency in several families (PMID: 28516040, 9600456). This variant has been observed in several individuals with CPT2 specific enzyme activity <35% of normal, a finding that is highly specific for CPT2 deficiency (PMID: 23700290, 9600456, 28516040, 18363739). ClinVar contains an entry for this variant (Variation ID: 8958). Experimental studies have shown that this missense change results in significantly decreased CPT2 protein expression (PMID: 9600456). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV001004159 SCV001162925 pathogenic Carnitine palmitoyltransferase II deficiency, infantile; Carnitine palmitoyltransferase II deficiency, lethal neonatal criteria provided, single submitter clinical testing
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV001270097 SCV001448915 pathogenic Seizures; Abnormality of the nervous system 2016-05-18 criteria provided, single submitter clinical testing
Beijing Key Laboratry for Genetics of Birth Defects,Beijing Children's Hospital RCV000009517 SCV001739497 likely pathogenic Carnitine palmitoyltransferase II deficiency, infantile 2020-02-28 criteria provided, single submitter clinical testing
OMIM RCV000009517 SCV000029735 pathogenic Carnitine palmitoyltransferase II deficiency, infantile 2007-08-21 no assertion criteria provided literature only
GeneReviews RCV000202462 SCV000153664 pathogenic Carnitine palmitoyltransferase II deficiency 2017-03-16 no assertion criteria provided literature only
OMIM RCV000009518 SCV000493926 pathogenic Carnitine palmitoyltransferase II deficiency, myopathic, stress-induced 2007-08-21 no assertion criteria provided literature only

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