Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001898461 | SCV002166952 | uncertain significance | not provided | 2024-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 397 of the LZTR1 protein (p.Ser397Leu). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 1394166). 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 80%. 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 | RCV002334827 | SCV002644529 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-02-03 | criteria provided, single submitter | clinical testing | The p.S397L variant (also known as c.1190C>T), located in coding exon 11 of the LZTR1 gene, results from a C to T substitution at nucleotide position 1190. The serine at codon 397 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well 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. |
| Baylor Genetics | RCV004571559 | SCV005060688 | uncertain significance | Schwannomatosis 2 | 2023-12-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001898461 | SCV005391523 | uncertain significance | not provided | 2024-03-14 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |