Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center for Molecular Medicine, |
RCV001030049 | SCV001190572 | pathogenic | Autosomal recessive osteopetrosis 1 | 2019-05-10 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002552435 | SCV003440336 | pathogenic | not provided | 2024-01-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln372*) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with osteoporosis (PMID: 11532986, 21042819, 31501239). This variant is also known as C6078G. ClinVar contains an entry for this variant (Variation ID: 830066). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155339 | SCV003844917 | pathogenic | Osteopetrosis | 2023-02-17 | criteria provided, single submitter | clinical testing | Variant summary: TCIRG1 c.1114C>T (p.Gln372X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4.1e-06 in 244650 control chromosomes. c.1114C>T has been reported in the literature in individuals affected with Osteopetrosis and related phenotypes (Cao_2018, Sobacchi_2001, Wang_2020, Yang_2020, Yuan_2011). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV001030049 | SCV004205783 | pathogenic | Autosomal recessive osteopetrosis 1 | 2023-05-01 | criteria provided, single submitter | clinical testing |