ClinVar Miner

Submissions for variant NM_006019.4(TCIRG1):c.2008C>T (p.Arg670Ter)

gnomAD frequency: 0.00010  dbSNP: rs371263807
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666300 SCV000790569 pathogenic Autosomal recessive osteopetrosis 1 2017-03-29 criteria provided, single submitter clinical testing
Baylor Genetics RCV000666300 SCV000807565 pathogenic Autosomal recessive osteopetrosis 1 2024-03-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000819121 SCV000959764 pathogenic not provided 2024-01-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg670*) 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 (rs371263807, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with TCIRG1-related conditions (PMID: 11532986). ClinVar contains an entry for this variant (Variation ID: 551284). For these reasons, this variant has been classified as Pathogenic.
Center for Molecular Medicine, Children’s Hospital of Fudan University RCV000666300 SCV001190573 pathogenic Autosomal recessive osteopetrosis 1 2019-05-10 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000819121 SCV001249643 pathogenic not provided 2019-11-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001199854 SCV001370586 pathogenic Osteopetrosis 2020-05-29 criteria provided, single submitter clinical testing Variant summary: TCIRG1 c.2008C>T (p.Arg670X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 7.1e-05 in 184378 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in TCIRG1 causing Osteopetrosis (7.1e-05 vs 0.0016), allowing no conclusion about variant significance. c.2008C>T has been reported in the literature in individuals affected with Osteopetrosis (Sobacchi_2001, Yang_2018, Yu_2014, Wang_2018). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneDx RCV000819121 SCV003805505 pathogenic not provided 2023-02-25 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 24535484, 23721911, 31501239, 25525159, 32411386, 31589614, 31949009, 34545712, 11532986)
Natera, Inc. RCV000666300 SCV001456354 pathogenic Autosomal recessive osteopetrosis 1 2020-09-16 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.