Submissions for variant NM_006019.4(TCIRG1):c.1230del (p.Leu411fs)

dbSNP: rs2134454279

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001994685	SCV002229094	pathogenic	not provided	2024-01-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu411Cysfs*19) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal recessive osteopetrosis (PMID: 12507890). This variant is also known as 8521delG. ClinVar contains an entry for this variant (Variation ID: 1452936). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003471137	SCV004205777	pathogenic	Autosomal recessive osteopetrosis 1	2023-06-07	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003978445	SCV004793213	pathogenic	TCIRG1-related disorder	2023-10-18	no assertion criteria provided	clinical testing	The TCIRG1 c.1230delG variant is predicted to result in a frameshift and premature protein termination (p.Leu411Cysfs*19). In the literature this variant is referred to as 8521delG. This variant was reported in the homozygous state in an individual with osteopetrosis (Taranta et al. 2003. PubMed ID: 12507890). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in TCIRG1 are expected to be pathogenic. This variant is interpreted as pathogenic.