ClinVar Miner

Submissions for variant NM_001379200.1(TBX1):c.711C>T (p.His237=)

gnomAD frequency: 0.00009  dbSNP: rs200021644
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000618363 SCV000736296 uncertain significance Cardiovascular phenotype 2016-09-01 criteria provided, single submitter clinical testing The c.684C>T variant (also known as p.H228H), located in coding exon 4 of the TBX1 gene, results from a C to T substitution at nucleotide position 684. This nucleotide substitution does not change the histidine at codon 228. However, this change occurs in the last base pair of coding exon 4, which makes it likely to have some effect on normal mRNA splicing. This variant was previously reported in the SNPDatabase as rs200021644. Based on data from ExAC, the T allele has an overall frequency of approximately 0.012% (13/105512). This nucleotide position is poorly conserved in available vertebrate species, and T is the reference nucleotide in numerous species. Using two different splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site by BDGP and strengthen the efficiency of the native splice donor site by ESEfinder; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001062273 SCV001227060 uncertain significance DiGeorge syndrome 2023-11-19 criteria provided, single submitter clinical testing This sequence change affects codon 228 of the TBX1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the TBX1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs200021644, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TBX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 518811). 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 is not likely to affect RNA splicing. 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.
PreventionGenetics, part of Exact Sciences RCV003892394 SCV004709242 likely benign TBX1-related disorder 2020-08-10 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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