ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs1489993984
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Total submissions: 5
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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
Invitae 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 Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine 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 det ect ed in her spouse (Mr. SAJJAN FUFUTE; Case ID: 20400109899).
Baylor Genetics RCV000673534 SCV004205804 pathogenic Autosomal recessive osteopetrosis 1 2022-12-19 criteria provided, single submitter clinical testing
Natera, Inc. RCV000673534 SCV002094911 pathogenic Autosomal recessive osteopetrosis 1 2021-08-30 no assertion criteria provided clinical testing

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