Submissions for variant NM_006019.4(TCIRG1):c.196+1G>T

dbSNP: rs2134432498

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001379497	SCV001577309	likely pathogenic	not provided	2022-11-12	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1068056). Disruption of this splice site has been observed in individual(s) with osteopetrosis (PMID: 25018813). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 3 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).
Molecular Lab, Department of Haematology, Christian Medical College	RCV002246359	SCV002516024	pathogenic	Autosomal recessive osteopetrosis 1	2022-05-20	criteria provided, single submitter	clinical testing
Neuberg Centre For Genomic Medicine, NCGM	RCV002246359	SCV004175843	likely pathogenic	Autosomal recessive osteopetrosis 1	2023-02-14	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV002246359	SCV004205780	pathogenic	Autosomal recessive osteopetrosis 1	2024-01-16	criteria provided, single submitter	clinical testing