ClinVar Miner

Submissions for variant NM_006019.4(TCIRG1):c.2236+1G>A

gnomAD frequency: 0.00004  dbSNP: rs1475338876
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674460 SCV000799799 pathogenic Autosomal recessive osteopetrosis 1 2018-05-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001062506 SCV001227312 pathogenic not provided 2023-11-24 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 18 of the TCIRG1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TCIRG1 are known to be pathogenic (PMID: 10888887, 10942435, 11532986, 19448635). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with osteopetrosis (PMID: 11532986, 12552563, 20424301, 25018813, 31319225). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as G11279A or IVS18+1G>A. ClinVar contains an entry for this variant (Variation ID: 558226). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center RCV000674460 SCV001428496 pathogenic Autosomal recessive osteopetrosis 1 2018-11-01 criteria provided, single submitter clinical testing This variant was identified as homozygous
Revvity Omics, Revvity RCV000674460 SCV002018946 pathogenic Autosomal recessive osteopetrosis 1 2021-09-06 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000674460 SCV002786488 pathogenic Autosomal recessive osteopetrosis 1 2022-03-05 criteria provided, single submitter clinical testing
Baylor Genetics RCV000674460 SCV004205728 pathogenic Autosomal recessive osteopetrosis 1 2024-02-12 criteria provided, single submitter clinical testing
GeneDx RCV001062506 SCV005078778 pathogenic not provided 2024-02-14 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Also known as IVS18+1G>A; This variant is associated with the following publications: (PMID: 31319225, 25525159, 30898715, 25018813, 25330538, 31794943, 31589614, 34671977, 11532986, 12552563)
Natera, Inc. RCV000674460 SCV002092936 pathogenic Autosomal recessive osteopetrosis 1 2020-12-11 no assertion criteria provided clinical testing

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