ClinVar Miner

Submissions for variant NM_001876.4(CPT1A):c.100T>C (p.Ser34Pro)

dbSNP: rs398123653
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000723488 SCV000111793 uncertain significance not provided 2018-07-20 criteria provided, single submitter clinical testing
GeneDx RCV000723488 SCV000589320 likely pathogenic not provided 2023-02-10 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35822099)
Invitae RCV000693588 SCV000821463 pathogenic Carnitine palmitoyl transferase 1A deficiency 2023-08-31 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 34 of the CPT1A protein (p.Ser34Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with CPT1A-related disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 93971). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant disrupts the p.Ser34 amino acid residue in CPT1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). 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.
Fulgent Genetics, Fulgent Genetics RCV000693588 SCV000894655 uncertain significance Carnitine palmitoyl transferase 1A deficiency 2018-10-31 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003407458 SCV004107766 uncertain significance CPT1A-related disorder 2023-09-20 criteria provided, single submitter clinical testing The CPT1A c.100T>C variant is predicted to result in the amino acid substitution p.Ser34Pro. This variant has been detected in the homozygous state in multiple individuals through expanded metabolic screening (EMS), including in three unaffected homozygous adults ascertained during family follow up studies (Table 1, Bernhardt et al. 2022. PubMed ID: 35822099). In the 22 cases described, none were reported to have episodes of significant metabolic decompensation (age range 5 weeks to 33 years), and for 10 cases no dietary management was included as part of treatment. In vitro functional study of cells from an unaffected homozygous individual showed residual CPT1A enzyme activity at ~26% of controls (Bernhardt et al. 2022. PubMed ID: 35822099). This variant has not been reported in a large population database ( but is predicted to be common in the Micronesian population based on the number of homozygous individuals detected through EMS (Bernhardt et al. 2022. PubMed ID: 35822099). Although we suspect this variant is likely benign, without formal fasting studies it is unclear if this variant could result in mild clinical consequences. At this time, the clinical significance of this variant is uncertain.

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