Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001230075 | SCV001402544 | uncertain significance | Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 66 of the TREX1 protein (p.Lys66Arg). This variant is present in population databases (rs188508043, gnomAD 0.03%). This missense change has been observed in individual(s) with Aicardi Goutières syndrome (PMID: 24183309). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 957146). 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. 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 |
RCV001751447 | SCV001986209 | uncertain significance | not provided | 2020-11-25 | criteria provided, single submitter | clinical testing | Observed in an individual with Aicardi-Goutieres syndrome who harbored a second TREX1 variant; however phase was unknown (Rice et al., 2013); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24183309, 23979357) |
| Ambry Genetics | RCV002563178 | SCV003718060 | uncertain significance | Inborn genetic diseases | 2022-03-14 | criteria provided, single submitter | clinical testing | The c.197A>G (p.K66R) alteration is located in exon 2 (coding exon 1) of the TREX1 gene. This alteration results from a A to G substitution at nucleotide position 197, causing the lysine (K) at amino acid position 66 to be replaced by an arginine (R). Based on data from gnomAD, the G allele has an overall frequency of 0.01% (18/282460) total alleles studied. The highest observed frequency was 0.03% (10/35426) of Latino alleles. This amino acid position is highly conserved in available vertebrate species. The in silico prediction for this alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |