ClinVar Miner

Submissions for variant NM_014714.4(IFT140):c.1377G>A (p.Trp459Ter)

gnomAD frequency: 0.00006  dbSNP: rs140039128
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000704469 SCV000833420 pathogenic Saldino-Mainzer syndrome 2023-10-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp459*) in the IFT140 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IFT140 are known to be pathogenic (PMID: 22503633, 23418020, 24009529, 26216056). This variant is present in population databases (rs140039128, gnomAD 0.2%). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 26216056). ClinVar contains an entry for this variant (Variation ID: 580815). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV001535954 SCV001752615 pathogenic Saldino-Mainzer syndrome; Retinitis pigmentosa 80 2022-03-21 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001724143 SCV001950285 likely pathogenic Retinitis pigmentosa 2021-04-01 criteria provided, single submitter curation The p.Trp459Ter variant in IFT140 was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PVS1, PM2. Based on this evidence we have classified this variant as Likely Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab.
PreventionGenetics, part of Exact Sciences RCV003411642 SCV004114463 pathogenic IFT140-related condition 2024-02-20 criteria provided, single submitter clinical testing The IFT140 c.1377G>A variant is predicted to result in premature protein termination (p.Trp459*). This variant has been reported to be pathogenic for autosomal recessive retinitis pigmentosa and the autosomal dominant polycystic kidney-spectrum phenotype (Xu et al. 2015. PubMed ID: 26216056; Senum et al. 2022. PubMed ID: 34890546). This variant is reported in 0.22% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. Nonsense variants in IFT140 are expected to be pathogenic. This variant is interpreted as pathogenic for both autosomal dominant and autosomal recessive IFT140-related disorders.

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.