Submissions for variant NM_000098.3(CPT2):c.1493G>A (p.Arg498His)

gnomAD frequency: 0.00001  dbSNP: rs776645157

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001293591	SCV001482207	uncertain significance	not specified	2021-12-03	criteria provided, single submitter	clinical testing	Variant summary: CPT2 c.1493G>A (p.Arg498His) results in a non-conservative amino acid change located in the Choline/carnitine acyltransferase domain (IPR039551) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 248508 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1493G>A in individuals affected with Carnitine Palmitoyltransferase II Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. No other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV002486105	SCV002790567	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	2021-07-05	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001830115	SCV003785349	uncertain significance	Carnitine palmitoyltransferase II deficiency	2021-12-31	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 498 of the CPT2 protein (p.Arg498His). This variant is present in population databases (rs776645157, gnomAD 0.002%). 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: 997927). 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 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.
Genome-Nilou Lab	RCV003449844	SCV004179561	uncertain significance	Encephalopathy, acute, infection-induced, susceptibility to, 4	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003449841	SCV004179562	uncertain significance	Carnitine palmitoyl transferase II deficiency, severe infantile form	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003449843	SCV004179563	uncertain significance	Carnitine palmitoyl transferase II deficiency, neonatal form	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003449842	SCV004179565	uncertain significance	Carnitine palmitoyl transferase II deficiency, myopathic form	2023-04-11	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001830115	SCV002090309	uncertain significance	Carnitine palmitoyltransferase II deficiency	2020-06-01	no assertion criteria provided	clinical testing