ClinVar Miner

Submissions for variant NM_000098.3(CPT2):c.452G>A (p.Arg151Gln) (rs515726177)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000492874 SCV000583282 likely pathogenic not provided 2018-12-05 criteria provided, single submitter clinical testing The R151Q variant has been reported previously in the homozygous state in an individual withinfantile-onset CPT2 deficiency (Thuillier et al., 2003). The R151Q variant has been reportedpreviously in three individuals who also harbored the S113L variant. Ages of onset for these threeaffected individuals were 47, 17, and 15 years old (Corti et al., 2008). The R151Q variant is notobserved at a significant frequency in large population cohorts (Lek et al., 2016; 1000 GenomesConsortium et al., 2015; Exome Variant Server). The R151Q variant is a semi-conservative aminoacid substitution, which may impact secondary protein structure as these residues differ in someproperties. This substitution occurs at a position that is conserved across species. In silico analysispredicts this variant is probably damaging to the protein structure/function. In summary, this variant islikely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV000202567 SCV000823652 pathogenic Carnitine palmitoyltransferase II deficiency 2018-06-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 151 of the CPT2 protein (p.Arg151Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs515726177, ExAC 0.003%). This variant has been observed to be homozygous or in combination with another CPT2 variant in individuals affected with carnitine palmitoyltransferase 2 (CPT2) deficiency (PMID: 9758712, 12673791, 14605500, 21913903), and has been shown to segregate with disease in a family (PMID: 17936304). ClinVar contains an entry for this variant (Variation ID: 130889). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000202567 SCV000153669 pathogenic Carnitine palmitoyltransferase II deficiency 2017-03-16 no assertion criteria provided literature only
Counsyl RCV000984253 SCV001132376 likely pathogenic Carnitine palmitoyltransferase II deficiency, infantile 2019-07-18 no assertion criteria provided clinical testing

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