Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000548200 | SCV000638091 | pathogenic | Carnitine palmitoyl transferase 1A deficiency | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 10 of the CPT1A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CPT1A are known to be pathogenic (PMID: 16169268). This variant is present in population databases (rs148059333, gnomAD 0.09%). Disruption of this splice site has been observed in individuals with carnitine palmitoyltransferase 1A deficiency (PMID: 27066452; Invitae). ClinVar contains an entry for this variant (Variation ID: 371246). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Laboratory for Molecular Medicine, |
RCV000548200 | SCV000966886 | pathogenic | Carnitine palmitoyl transferase 1A deficiency | 2017-08-07 | criteria provided, single submitter | clinical testing | The c.1163+1G>A (NM_001876.3 c.1163+1G>A) variant in CPT1A has been reported in a compound heterozygous individual with carnitine palmitoyltransferase I (CPT I) deficiency (Choi 2016).This variant has been identified in 0.092% (9/9,828) of Ashkenazi Jewish chromosomes by the Genome Aggregation Database (gnomAD, http:// gnomAD.broadinstitute.org; dbSNP rs148059333). Although this variant has been se en in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Biallelic loss of function of the CPT 1A gene is associated with CPT I deficiency. In summary, the c.1163+1G>A variant meets our criteria to be classified as pathogenic for CPT I deficiency in an au tosomal recessive manner based upon its predicted null effect and occurrence in an affected individual. |
Baylor Genetics | RCV000548200 | SCV001163324 | pathogenic | Carnitine palmitoyl transferase 1A deficiency | criteria provided, single submitter | clinical testing | ||
Counsyl | RCV000548200 | SCV000486780 | likely pathogenic | Carnitine palmitoyl transferase 1A deficiency | 2016-08-04 | no assertion criteria provided | clinical testing | |
Natera, |
RCV000548200 | SCV001456363 | pathogenic | Carnitine palmitoyl transferase 1A deficiency | 2020-09-16 | no assertion criteria provided | clinical testing |