Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002015458 | SCV002280641 | uncertain significance | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 8 of the LZTR1 protein (p.Gly8Arg). This variant is present in population databases (rs575193991, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with LZTR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1496147). 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 LZTR1 protein function with a negative predictive value of 95%. 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 | RCV002443022 | SCV002734848 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-12-15 | criteria provided, single submitter | clinical testing | The p.G8R variant (also known as c.22G>C), located in coding exon 1 of the LZTR1 gene, results from a G to C substitution at nucleotide position 22. The glycine at codon 8 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| St. |
RCV003230291 | SCV003928087 | uncertain significance | Noonan syndrome 10 | 2023-03-31 | criteria provided, single submitter | clinical testing | The LZTR1 c.22G>C (p.Gly8Arg) missense change has a maximum frequency of 0.023% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Noonan syndrome or schwannomatosis. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.?? |
| Gene |
RCV002015458 | SCV003936670 | uncertain significance | not provided | 2022-12-29 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Baylor Genetics | RCV003464369 | SCV004191244 | uncertain significance | Schwannomatosis 2 | 2023-09-29 | criteria provided, single submitter | clinical testing |