Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Myriad Genetics, |
RCV001810546 | SCV002060129 | uncertain significance | Autosomal recessive osteopetrosis 1 | 2021-11-03 | criteria provided, single submitter | clinical testing | NM_006019.3(TCIRG1):c.117+4A>C is an intronic variant classified as a variant of uncertain significance in the context of autosomal recessive osteopetrosis type 1. c.117+4A>C has been observed in cases with relevant disease (PMID: 30537558). Functional assessments of this variant are not available in the literature. c.117+4A>C has been observed in population frequency databases (gnomAD: SAS 0.03%). In summary, there is insufficient evidence to classify NM_006019.3(TCIRG1):c.117+4A>C as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. |
Labcorp Genetics |
RCV001885295 | SCV002232458 | pathogenic | not provided | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 2 of the TCIRG1 gene. It does not directly change the encoded amino acid sequence of the TCIRG1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs751881962, gnomAD 0.03%). This variant has been observed in individual(s) with TCIRG1-related conditions (PMID: 30537558). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1334165). 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. This variant disrupts the c.117+4 nucleotide in the TCIRG1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 10942435, 15300850, 19507210, 24989235). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV001810546 | SCV004205785 | likely pathogenic | Autosomal recessive osteopetrosis 1 | 2024-02-05 | criteria provided, single submitter | clinical testing |