Submissions for variant NM_000098.3(CPT2):c.1784del (p.Pro595fs)

dbSNP: rs760255368

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000699884	SCV000828614	pathogenic	Carnitine palmitoyltransferase II deficiency	2025-01-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro595Glnfs*3) in the CPT2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 64 amino acid(s) of the CPT2 protein. This variant is present in population databases (rs760255368, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with CPT2 deficiency (PMID: 18550408; internal data). ClinVar contains an entry for this variant (Variation ID: 577198). This variant disrupts the p.Tyr628 amino acid residue in CPT2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8651281, 9600456). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000699884	SCV000919249	pathogenic	Carnitine palmitoyltransferase II deficiency	2018-08-24	criteria provided, single submitter	clinical testing	Variant summary: CPT2 c.1784delC (p.Pro595GlnfsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4.1e-06 in 246268 control chromosomes (gnomAD). c.1784delC has been reported in the literature in individuals affected with Carnitine Palmitoyltransferase II Deficiency (Isackson_2008, Wang_2013). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneDx	RCV001574131	SCV001800891	likely pathogenic	not provided	2021-05-11	criteria provided, single submitter	clinical testing	Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 64 amino acids are lost and replaced with 2 incorrect amino acids; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 22899091, 18550408)
Genome-Nilou Lab	RCV003453477	SCV004178311	likely pathogenic	Carnitine palmitoyl transferase II deficiency, severe infantile form	2023-04-11	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003472233	SCV004211064	pathogenic	Encephalopathy, acute, infection-induced, susceptibility to, 4	2023-12-19	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005021088	SCV005653728	likely 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	2024-03-04	criteria provided, single submitter	clinical testing