Submissions for variant NM_006019.4(TCIRG1):c.346C>T (p.Gln116Ter)

gnomAD frequency: 0.00001  dbSNP: rs1338631330

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000798499	SCV000938118	pathogenic	not provided	2023-09-05	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 552835). This variant has not been reported in the literature in individuals affected with TCIRG1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.008%). This sequence change creates a premature translational stop signal (p.Gln116*) 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).
PreventionGenetics, part of Exact Sciences	RCV003411576	SCV004106769	likely pathogenic	TCIRG1-related disorder	2023-01-23	criteria provided, single submitter	clinical testing	The TCIRG1 c.346C>T variant is predicted to result in premature protein termination (p.Gln116*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0082% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-67810259-C-T). Nonsense variants in TCIRG1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Baylor Genetics	RCV000668174	SCV004205803	pathogenic	Autosomal recessive osteopetrosis 1	2022-12-28	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000668174	SCV005044035	pathogenic	Autosomal recessive osteopetrosis 1	2024-01-29	criteria provided, single submitter	clinical testing	PVS1 PM2 PM3_Supporting, PP3
GeneDx	RCV000798499	SCV005379916	uncertain significance	not provided	2023-12-18	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; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics	RCV000668174	SCV005684237	likely pathogenic	Autosomal recessive osteopetrosis 1	2024-04-09	criteria provided, single submitter	clinical testing
Counsyl	RCV000668174	SCV000792732	likely pathogenic	Autosomal recessive osteopetrosis 1	2017-07-11	no assertion criteria provided	clinical testing	This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact [e-mail].