Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000671340 | SCV000796304 | likely pathogenic | Autosomal recessive osteopetrosis 1 | 2017-12-11 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001199944 | SCV001370740 | likely pathogenic | Osteopetrosis | 2020-05-28 | criteria provided, single submitter | clinical testing | Variant summary: TCIRG1 c.1024G>T (p.Glu342X) 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. The variant allele was found at a frequency of 4.1e-06 in 245566 control chromosomes (gnomAD). c.1024G>T has been reported in the literature in one individual affected with Osteopetrosis (Kornak_2000). 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. One ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV002531278 | SCV003440335 | pathogenic | not provided | 2023-06-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu342*) 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 present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with osteopetrosis (PMID: 10942435). ClinVar contains an entry for this variant (Variation ID: 555504). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000671340 | SCV005052947 | likely pathogenic | Autosomal recessive osteopetrosis 1 | 2024-02-17 | criteria provided, single submitter | clinical testing |