Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001956449 | SCV002245950 | pathogenic | not provided | 2023-12-17 | criteria provided, single submitter | clinical testing | This sequence change affects codon 210 of the TCIRG1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the TCIRG1 protein. This variant also falls at the last nucleotide of exon 6, which is part of the consensus splice site for this exon. 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 variant has been observed in individual(s) with osteopetrosis (PMID: 30539151, 31111556). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1458586). Studies have shown that this variant alters TCIRG1 gene expression (PMID: 31111556). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003471190 | SCV004205754 | pathogenic | Autosomal recessive osteopetrosis 1 | 2023-08-02 | criteria provided, single submitter | clinical testing |