ClinVar Miner

Submissions for variant NM_000098.3(CPT2):c.149C>A (p.Pro50His) (rs28936375)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHLA Center for Personalized Medicine,Children's Hospital, Los Angeles RCV000735345 SCV000854499 pathogenic Pancytopenia; Arthritis; Dysautonomia; Gastrointestinal dysmotility; Polyarticular arthritis; Sinus tachycardia; Chronic pain; Inappropriate sinus tachycardia criteria provided, single submitter clinical testing
Counsyl RCV000009512 SCV000220135 pathogenic Carnitine palmitoyltransferase II deficiency, infantile 2014-03-02 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000440440 SCV000700664 pathogenic not provided 2016-12-13 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762941 SCV000893364 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
GeneDx RCV000440440 SCV000512762 pathogenic not provided 2018-04-18 criteria provided, single submitter clinical testing P50H is a common CPT2 pathogenic variant found in approximately 6.5% of mutant alleles in patients with the adult myopathic form of carnitine palmitoyltransferase II (CPT2) deficiency (Bonnefont et al., 2004). Expression of P50H in COS cells found that it is associated with 16.7% residual carnitine palmitoyltransferase II enzyme activity compared to wild type (Wataya et al. 1998). In summary, we interpret P50H as pathogenic.
GeneReviews RCV000202440 SCV000153655 pathogenic Carnitine palmitoyltransferase II deficiency 2014-05-15 no assertion criteria provided literature only
Integrated Genetics/Laboratory Corporation of America RCV000202440 SCV000695405 pathogenic Carnitine palmitoyltransferase II deficiency 2017-07-13 criteria provided, single submitter clinical testing Variant summary: The CPT2 c.149C>A (p.Pro50His) variant involves the alteration of a conserved nucleotide and 4/4 in silico tools (SNPsandGO not captured due to low reliability index) predict a damaging outcome. This variant was found in 2/11728 control chromosomes at a frequency of 0.0001705, which does not exceed the estimated maximal expected allele frequency of a pathogenic CPT2 variant (0.0015811). Multiple publications cite the variant in compound heterozygote affected individuals, which were found to have low CPT II activity. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000202440 SCV000632589 pathogenic Carnitine palmitoyltransferase II deficiency 2017-09-18 criteria provided, single submitter clinical testing This sequence change replaces proline with histidine at codon 50 of the CPT2 protein (p.Pro50His). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and histidine. While this variant is present in population databases (rs28936375), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in several individuals affected with CPT2 deficiency. In all the homozygous individuals and most of the compound heterozygotes it has been associated with the late-onset form of the disease (PMID: 7711730, 10090476, 12410208, 12707442, 16996287, 17936304). ClinVar contains an entry for this variant (Variation ID: 8954). Experimental studies have shown that this missense change causes a significant decrease in CPT II activity by altering the stability of the CPT II protein (PMID: 7711730). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000009511 SCV000029729 pathogenic Carnitine palmitoyltransferase II deficiency, myopathic, stress-induced 2002-11-01 no assertion criteria provided literature only
OMIM RCV000009512 SCV000029730 pathogenic Carnitine palmitoyltransferase II deficiency, infantile 2002-11-01 no assertion criteria provided literature only

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