ClinVar Miner

Submissions for variant NM_000098.3(CPT2):c.1189G>A (p.Val397Ile)

gnomAD frequency: 0.00004  dbSNP: rs201745292
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001058627 SCV001223212 uncertain significance Carnitine palmitoyltransferase II deficiency 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 397 of the CPT2 protein (p.Val397Ile). This variant is present in population databases (rs201745292, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with CPT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 853753). 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. 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.
Fulgent Genetics, Fulgent Genetics RCV002482031 SCV002775145 uncertain significance 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 2021-11-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002509603 SCV002819331 uncertain significance not specified 2022-12-08 criteria provided, single submitter clinical testing Variant summary: CPT2 c.1189G>A (p.Val397Ile) results in a conservative amino acid change located in the Choline/carnitine acyltransferase domain of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 251284 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in CPT2 causing Carnitine Palmitoyltransferase II Deficiency (4.4e-05 vs 0.0016), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1189G>A in individuals affected with Carnitine Palmitoyltransferase II Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab RCV003455267 SCV004179482 uncertain significance Encephalopathy, acute, infection-induced, susceptibility to, 4 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003455264 SCV004179483 uncertain significance Carnitine palmitoyl transferase II deficiency, severe infantile form 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003455266 SCV004179484 uncertain significance Carnitine palmitoyl transferase II deficiency, neonatal form 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003455265 SCV004179485 uncertain significance Carnitine palmitoyl transferase II deficiency, myopathic form 2023-04-11 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV003480936 SCV004227845 uncertain significance not provided 2023-02-10 criteria provided, single submitter clinical testing BP4_strong
Natera, Inc. RCV001058627 SCV002090293 uncertain significance Carnitine palmitoyltransferase II deficiency 2020-02-10 no assertion criteria provided clinical testing

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