Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000169420 | SCV000220828 | likely pathogenic | Glutaric aciduria, type 1 | 2014-10-21 | criteria provided, single submitter | literature only | |
Eurofins Ntd Llc |
RCV000727581 | SCV000854824 | pathogenic | not provided | 2018-08-17 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000169420 | SCV002156946 | pathogenic | Glutaric aciduria, type 1 | 2023-02-07 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 189030). 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. This variant is also known as IVS3+1G>A. This sequence change affects a donor splice site in intron 4 of the GCDH 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 GCDH are known to be pathogenic (PMID: 10699052, 11854167, 16602100). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with glutaric acidemia type I (PMID: 11058907). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. |