ClinVar Miner

Submissions for variant NM_000254.3(MTR):c.2474-1G>C

gnomAD frequency: 0.00001  dbSNP: rs757963570
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
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001195906 SCV001366330 pathogenic Methylcobalamin deficiency type cblG 2019-04-08 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP3.
Invitae RCV001195906 SCV004285450 pathogenic Methylcobalamin deficiency type cblG 2024-01-18 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 23 of the MTR 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 MTR are known to be pathogenic (PMID: 9683607, 12068375). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with cobalamin G deficiency (PMID: 25526710; Invitae). ClinVar contains an entry for this variant (Variation ID: 930329). 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.

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.