Submissions for variant NM_000098.3(CPT2):c.1598T>C (p.Val533Ala)

gnomAD frequency: 0.00048  dbSNP: rs144703247

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000185827	SCV000238776	benign	not specified	2014-09-11	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080230	SCV000632591	likely benign	Carnitine palmitoyltransferase II deficiency	2024-01-31	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000711322	SCV000841663	benign	not provided	2019-06-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000185827	SCV002500707	uncertain significance	not specified	2022-03-03	criteria provided, single submitter	clinical testing	Variant summary: CPT2 c.1598T>C (p.Val533Ala) results in a non-conservative amino acid change located in the Choline/carnitine acyltransferase domain (IPR039551) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00048 in 245266 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in CPT2 causing Carnitine Palmitoyltransferase II Deficiency (0.00048 vs 0.0016), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1598T>C 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 and classified the variant as benign (n=1) and likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000711322	SCV004564967	likely benign	not provided	2023-09-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003917702	SCV004728884	benign	CPT2-related disorder	2019-05-03	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).