ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs777785526
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Total submissions: 7
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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 2023-10-10 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

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