Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001983454 | SCV002269579 | uncertain significance | Achondrogenesis, type IA | 2022-09-12 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with glutamic acid at codon 111 of the TRIP11 protein (p.Lys111Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs776314213, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TRIP11-related conditions. ClinVar contains an entry for this variant (Variation ID: 1489824). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TRIP11 protein function. 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. |
| Ambry Genetics | RCV004045303 | SCV004971599 | uncertain significance | Inborn genetic diseases | 2023-10-27 | criteria provided, single submitter | clinical testing | The c.331A>G (p.K111E) alteration is located in exon 4 (coding exon 4) of the TRIP11 gene. This alteration results from a A to G substitution at nucleotide position 331, causing the lysine (K) at amino acid position 111 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |