Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001233425 | SCV001406018 | uncertain significance | Achondrogenesis, type IA | 2019-11-14 | criteria provided, single submitter | clinical testing | 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. 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"). This variant has not been reported in the literature in individuals with TRIP11-related conditions. This variant is present in population databases (rs763206653, ExAC 0.01%). This sequence change replaces arginine with cysteine at codon 1576 of the TRIP11 protein (p.Arg1576Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV003448379 | SCV004176648 | uncertain significance | Goldblatt syndrome | 2023-02-14 | criteria provided, single submitter | clinical testing | The missense c.4726C>T(p.Arg1576Cys) variant in TRIP11 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is reported with an allele frequency of 0.0004% in the gnomAD exomes database and is novel (not in any individuals) in 1000 Genomes database. This variant has been reported to the ClinVar database as Uncertain significance. The amino acid change p.Arg1576Cys in TRIP11 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Arg at position 1576 is changed to a Cys changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS). |