ClinVar Miner

Submissions for variant NM_133259.4(LRPPRC):c.469+1G>A

dbSNP: rs1060499785
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000454266 SCV000538048 likely pathogenic Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type 2016-03-30 criteria provided, single submitter clinical testing The c.469+1G>A splice-donor variant in the LRPPRC gene has been not been previously reported in published literature and is absent from the population databases (ESP; 1000 Genomes; ExAC). This variant is located within the canonical splice site of intron 3, and in silico algorithms predict this variant will cause abnormal splicing (Human Splice Finder = Broken WT Donor Site). Multiple splice variants located downstream of this c.469+1G>A variant have been reported as pathogenic by reputable diagnostic laboratories (c.864+2 T>C, c.1920+1 G>T). Therefore, this collective evidence supports the classification of the c.469+1G>A as a recessive *Likely pathogenic (see recommendation) variant for Leigh Syndrome.
Invitae RCV002522742 SCV003459351 likely pathogenic not provided 2023-04-20 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 402234). This variant has not been reported in the literature in individuals affected with LRPPRC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 3 of the LRPPRC 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 LRPPRC are known to be pathogenic (PMID: 26510951).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.