Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002026204 | SCV002300103 | uncertain significance | not provided | 2023-11-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 471 of the LZTR1 protein (p.Arg471Pro). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 1513508). 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 | RCV002389035 | SCV002696526 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-02-27 | criteria provided, single submitter | clinical testing | The p.R471P variant (also known as c.1412G>C), located in coding exon 13 of the LZTR1 gene, results from a G to C substitution at nucleotide position 1412. The arginine at codon 471 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003471273 | SCV004191257 | uncertain significance | Schwannomatosis 2 | 2023-09-19 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002026204 | SCV005333126 | uncertain significance | not provided | 2023-04-11 | 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 |