Submissions for variant NM_000098.3(CPT2):c.577C>T (p.Arg193Cys)

dbSNP: rs375968699

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000305853	SCV000341267	likely benign	not specified	2016-04-11	criteria provided, single submitter	clinical testing
Invitae	RCV000635374	SCV000756783	likely benign	Carnitine palmitoyltransferase II deficiency	2024-01-31	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001508866	SCV001715287	uncertain significance	not provided	2020-06-25	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000305853	SCV002512028	likely benign	not specified	2022-04-25	criteria provided, single submitter	clinical testing	Variant summary: CPT2 c.577C>T (p.Arg193Cys) 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 0.00037 in 251426 control chromosomes, predominantly at a frequency of 0.002 within the East Asian subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1.3 fold of the estimated maximal expected allele frequency for a pathogenic variant in CPT2 causing Carnitine Palmitoyltransferase II Deficiency phenotype (0.0016), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.577C>T in individuals affected with Carnitine Palmitoyltransferase II Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and a predominant consensus as likely benign (n=3) (VUS, n=1). Based on the evidence outlined above, the variant was classified as likely benign.
Revvity Omics, Revvity	RCV001508866	SCV003829973	uncertain significance	not provided	2022-03-22	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000635374	SCV001454119	likely benign	Carnitine palmitoyltransferase II deficiency	2020-02-14	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001508866	SCV001742142	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001508866	SCV001809168	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001508866	SCV001931698	likely pathogenic	not provided		no assertion criteria provided	clinical testing