ClinVar Miner

Submissions for variant NM_006019.4(TCIRG1):c.1297C>T (p.Gln433Ter)

gnomAD frequency: 0.00001  dbSNP: rs777785526
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000675173 SCV000373721 uncertain significance Autosomal recessive osteopetrosis 1 2017-04-27 criteria provided, single submitter clinical testing The TCIRG1 c.1297C>T (p.Gln433Ter) is a stop-gained variant that is predicted to result in an elongation of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The p.Gln433Ter variant is reported at a frequency of 0.00009 in the European (non-Finnish) population of the Exome Aggregation Consortium. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, the p.Gln433Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for osteopetrosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000675173 SCV000845331 pathogenic Autosomal recessive osteopetrosis 1 2018-08-07 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000675173 SCV001369862 likely pathogenic Autosomal recessive osteopetrosis 1 2018-11-06 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PM2,PP3,PP5.
Invitae RCV001241325 SCV001414337 pathogenic not provided 2023-12-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln433*) 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 (rs777785526, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with osteopetrosis (PMID: 11532986, 15300850). ClinVar contains an entry for this variant (Variation ID: 305804). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000675173 SCV004205731 pathogenic Autosomal recessive osteopetrosis 1 2023-11-30 criteria provided, single submitter clinical testing
Counsyl RCV000675173 SCV000800796 pathogenic Autosomal recessive osteopetrosis 1 2017-11-26 no assertion criteria provided clinical testing
Clinic of Clinical Immunology with Stem Cell Bank, Expert Centre for Rare Diseases - PID, University Hospital "Alexandrovska" RCV000675173 SCV002573406 pathogenic Autosomal recessive osteopetrosis 1 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.