Submissions for variant NM_000098.3(CPT2):c.236A>C (p.Lys79Thr)

gnomAD frequency: 0.00027  dbSNP: rs150888506

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000530003	SCV000632603	uncertain significance	Carnitine palmitoyltransferase II deficiency	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 79 of the CPT2 protein (p.Lys79Thr). This variant is present in population databases (rs150888506, gnomAD 0.1%). 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: 460433). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000626610	SCV000747311	uncertain significance	Genu valgum; Pes planus; Hyperextensibility of the finger joints; Generalized hypotonia; Myopathic facies; Hyperextensible hand joints; Hyperextensibility at elbow	2017-01-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000530003	SCV001252951	uncertain significance	Carnitine palmitoyltransferase II deficiency	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Pars Genome Lab	RCV001449651	SCV001652852	uncertain significance	Carnitine palmitoyl transferase II deficiency, severe infantile form	2021-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001571245	SCV001795677	uncertain significance	not provided	2024-02-23	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29429925, 27467583, 28404951, 27460824)
Revvity Omics, Revvity	RCV001571245	SCV003829976	uncertain significance	not provided	2023-05-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003403273	SCV004106040	uncertain significance	CPT2-related disorder	2022-11-10	criteria provided, single submitter	clinical testing	The CPT2 c.236A>C variant is predicted to result in the amino acid substitution p.Lys79Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.096% of alleles in individuals of Ashkenazi Jewish descent and 0.043% in in individuals of Non-Finnish European descent in gnomAD, including one homozygous individual (http://gnomad.broadinstitute.org/variant/1-53667997-A-C), which may be too common to be an unreported disease-causing variant. Although we suspect that this variant may be benign, at this time its clinical significance is uncertain due to the absence of conclusive functional and genetic evidence.
Genome-Nilou Lab	RCV003456089	SCV004179294	uncertain significance	Encephalopathy, acute, infection-induced, susceptibility to, 4	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001449651	SCV004179295	uncertain significance	Carnitine palmitoyl transferase II deficiency, severe infantile form	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003451159	SCV004179296	uncertain significance	Carnitine palmitoyl transferase II deficiency, neonatal form	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003451158	SCV004179297	uncertain significance	Carnitine palmitoyl transferase II deficiency, myopathic form	2023-04-11	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV001571245	SCV004229556	uncertain significance	not provided	2023-07-07	criteria provided, single submitter	clinical testing	Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools predict that this variant is not damaging.
Ambry Genetics	RCV004023832	SCV004849785	uncertain significance	Inborn genetic diseases	2023-10-26	criteria provided, single submitter	clinical testing	The c.236A>C (p.K79T) alteration is located in exon 3 (coding exon 3) of the CPT2 gene. This alteration results from a A to C substitution at nucleotide position 236, causing the lysine (K) at amino acid position 79 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc.	RCV000530003	SCV001454115	uncertain significance	Carnitine palmitoyltransferase II deficiency	2020-01-27	no assertion criteria provided	clinical testing