Submissions for variant NM_000098.3(CPT2):c.98del (p.Gln33fs)

gnomAD frequency: 0.00005  dbSNP: rs917744011

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588722	SCV000695407	pathogenic	Carnitine palmitoyltransferase II deficiency	2016-11-23	criteria provided, single submitter	clinical testing	Variant summary: The c.98delA (p.Gln33Argfs) variant in CPT2 gene is a frameshift change that results in the loss of the 589 amino acids of CPT (~90%). This change is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. The variant is absent from the large control population dataset of ExAC, but has been reported in at least 1 severely affected individual in compound heterozygosity with a known pathogenic variant (p.S113L) via published report. Taking together, the variant was classified as Pathogenic.
Invitae	RCV000588722	SCV001219804	pathogenic	Carnitine palmitoyltransferase II deficiency	2023-07-29	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 495549). This premature translational stop signal has been observed in individual(s) with clinical features of CPT2 deficiency (PMID: 21913903). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Gln33Argfs*40) in the CPT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CPT2 are known to be pathogenic (PMID: 16781677, 16996287).
GeneDx	RCV001569307	SCV001793355	pathogenic	not provided	2022-02-03	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30957255, 21913903)
Fulgent Genetics, Fulgent Genetics	RCV002483563	SCV002778553	pathogenic	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	2021-08-16	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000984252	SCV004179248	pathogenic	Carnitine palmitoyl transferase II deficiency, severe infantile form	2023-04-11	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003471935	SCV004211039	pathogenic	Encephalopathy, acute, infection-induced, susceptibility to, 4	2023-10-04	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001569307	SCV004225836	pathogenic	not provided	2022-07-11	criteria provided, single submitter	clinical testing	PP4, PM2, PM3, PVS1
Counsyl	RCV000984252	SCV001132375	likely pathogenic	Carnitine palmitoyl transferase II deficiency, severe infantile form	2015-07-28	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000588722	SCV001461210	pathogenic	Carnitine palmitoyltransferase II deficiency	2020-09-16	no assertion criteria provided	clinical testing