ClinVar Miner

Submissions for variant NM_006019.4(TCIRG1):c.1276C>T (p.Arg426Ter)

gnomAD frequency: 0.00001  dbSNP: rs1489993984
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000673534 SCV000798746 pathogenic Autosomal recessive osteopetrosis 1 2018-03-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001390428 SCV001592160 pathogenic not provided 2023-10-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg426*) in the TCIRG1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TCIRG1 are known to be pathogenic (PMID: 10888887, 10942435, 11532986, 19448635). This variant is present in population databases (no rsID available, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with osteopetrosis (PMID: 22231430, 24101165). ClinVar contains an entry for this variant (Variation ID: 557398). For these reasons, this variant has been classified as Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM RCV000673534 SCV004101554 pathogenic Autosomal recessive osteopetrosis 1 criteria provided, single submitter clinical testing The c.1276C>T (p.Arg426Ter) stop gained variant in TCIRG1 gene has been observed in individual(s) affected with osteopetrosis (Siddaiahgari et al., 2014; Pangrazio et al., 2012). Loss-of-function variants in TCIRG1 are known to be pathogenic (Kornak et al., 2000).This variant is reported with the allele frequency (0.006%) in the gnomAD and novel in 1000 genome database. This variant has been reported to the ClinVar database as Pathogenic. The nucleotide change c.1276C>T in TCIRG1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic. The observed variant has also been detected in her spouse.
Baylor Genetics RCV000673534 SCV004205804 pathogenic Autosomal recessive osteopetrosis 1 2024-03-27 criteria provided, single submitter clinical testing
Natera, Inc. RCV000673534 SCV002094911 pathogenic Autosomal recessive osteopetrosis 1 2021-08-30 no assertion criteria provided clinical testing

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.