Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000318300 | SCV000457628 | uncertain significance | Succinyl-CoA acetoacetate transferase deficiency | 2016-07-15 | criteria provided, single submitter | clinical testing | The OXCT1 c.1099+2T>C variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. A literature search was performed for the gene and cDNA change. No publications were found based on this search. This variant is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium despite being found in a region of good sequencing coverage; therefore, the variant is presumed to be rare. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of splice donor variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for succinyl-CoA:3-oxoacid CoA transferase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV000318300 | SCV003456791 | likely pathogenic | Succinyl-CoA acetoacetate transferase deficiency | 2023-05-23 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. ClinVar contains an entry for this variant (Variation ID: 353659). This variant has not been reported in the literature in individuals affected with OXCT1-related conditions. This variant is present in population databases (rs202242762, gnomAD 0.009%). This sequence change affects a donor splice site in intron 11 of the OXCT1 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 OXCT1 are known to be pathogenic (PMID: 8751852). |