ClinVar

Description

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 (http://gnomad.broadinstitute.org) 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.