Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000823293 | SCV000964147 | uncertain significance | Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome | 2018-08-14 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 172 of the TRNT1 protein (p.Gly172Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant has not been reported in the literature in individuals with TRNT1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |