Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV001290248 | SCV001477291 | likely pathogenic | Intellectual disability, X-linked, syndromic 33 | 2020-11-16 | criteria provided, single submitter | clinical testing | We identified the variant c.2590C>T, p.Arg864Trp in the gene TAF1 in hemizygous state. In the two affected brothers of the index we also identified the variant in hemizygous state, while the two unaffected brothers of the index carry the wildtype allele. The unaffected mother and the unaffected sister both are heterozygous for this variant. Thus the variant segregates with the disease in this family. The gnomAD z score of 5.49 for this gene is indicative of it being relatively intolerant to missense variation. The variant allele was not identified in control chromosomes (gnomAD). The in silico tools we use mostly assess the change as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic according to the ACMG classification system (Richards et al., 2015, PMID: 25741868). PM2, PP1_Moderate, PP2, PP3 |
Invitae | RCV003565477 | SCV004321739 | uncertain significance | not provided | 2023-09-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 864 of the TAF1 protein (p.Arg864Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TAF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 995989). 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 disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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. |