Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002378930 | SCV002685773 | uncertain significance | Cardiovascular phenotype | 2021-09-30 | criteria provided, single submitter | clinical testing | The p.H425R variant (also known as c.1274A>G), located in coding exon 8 of the TBX1 gene, results from an A to G substitution at nucleotide position 1274. The histidine at codon 425 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003103568 | SCV003286693 | uncertain significance | DiGeorge syndrome | 2023-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 425 of the TBX1 protein (p.His425Arg). 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 not been reported in the literature in individuals affected with TBX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1766125). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
Gene |
RCV003223757 | SCV003919377 | uncertain significance | not provided | 2022-10-24 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |