ClinVar Miner

Submissions for variant NM_001379200.1(TBX1):c.539G>A (p.Arg180Gln)

dbSNP: rs770313856
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001757093 SCV001996630 uncertain significance not provided 2019-11-20 criteria provided, single submitter clinical testing In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing and cause the adjacent exon to be out of frame. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV002540389 SCV003221722 uncertain significance DiGeorge syndrome 2022-10-17 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with TBX1-related conditions. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 171 of the TBX1 protein (p.Arg171Gln). This variant also falls at the last nucleotide of exon 4, 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. ClinVar contains an entry for this variant (Variation ID: 1310025). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.