Submissions for variant NM_000098.3(CPT2):c.921G>A (p.Met307Ile)

gnomAD frequency: 0.00005  dbSNP: rs745698305

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001324688	SCV001515652	uncertain significance	Carnitine palmitoyltransferase II deficiency	2022-07-29	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 307 of the CPT2 protein (p.Met307Ile). This variant is present in population databases (rs745698305, 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: 374946). 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.
GeneDx	RCV001775787	SCV002013946	uncertain significance	not provided	2021-04-08	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant does not alter protein structure/function
CeGaT Center for Human Genetics Tuebingen	RCV001775787	SCV002062810	uncertain significance	not provided	2021-10-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002480274	SCV002791742	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	2022-05-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003449042	SCV004179432	uncertain significance	Encephalopathy, acute, infection-induced, susceptibility to, 4	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000415722	SCV004179433	uncertain significance	Carnitine palmitoyl transferase II deficiency, severe infantile form	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003449041	SCV004179434	uncertain significance	Carnitine palmitoyl transferase II deficiency, neonatal form	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003449040	SCV004179435	uncertain significance	Carnitine palmitoyl transferase II deficiency, myopathic form	2023-04-11	criteria provided, single submitter	clinical testing
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000415722	SCV000493728	uncertain significance	Carnitine palmitoyl transferase II deficiency, severe infantile form	2015-07-24	no assertion criteria provided	clinical testing
Natera, Inc.	RCV001324688	SCV002090281	uncertain significance	Carnitine palmitoyltransferase II deficiency	2019-10-28	no assertion criteria provided	clinical testing