Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001767699 | SCV001999468 | uncertain significance | not provided | 2024-10-18 | criteria provided, single submitter | clinical testing | In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV001767699 | SCV002315441 | uncertain significance | not provided | 2025-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 519 of the LZTR1 protein (p.Arg519Gln). This variant is present in population databases (rs149502567, gnomAD 0.01%). 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: 1310585). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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 | RCV002405300 | SCV002704906 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-12-14 | criteria provided, single submitter | clinical testing | The p.R519Q variant (also known as c.1556G>A), located in coding exon 14 of the LZTR1 gene, results from a G to A substitution at nucleotide position 1556. The arginine at codon 519 is replaced by glutamine, an amino acid with highly similar 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. |
| Clinical Genomics Laboratory, |
RCV004558637 | SCV005047099 | uncertain significance | Noonan syndrome 2; Noonan syndrome 10 | 2023-12-20 | criteria provided, single submitter | clinical testing | The LZTR1 c.1556G>A (p.Arg519Gln) variant was identified at a near heterozygous allelic fraction of 48.63%, a frequency which may be consistent with it being of germline origin. This variant, to our knowledge, has not been reported in the medical literature. This variant has been reported in the ClinVar database as a variant of uncertain significance by multiple submitters (ClinVar ID: 1310585). This variant is only observed on 27/1,601,696 alleles in the general population (gnomAD v.4.0.0), indicating it is not a common variant. Computational predictors suggest that the variant does not impact LZTR1 function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time. |
| Baylor Genetics | RCV004571076 | SCV005060598 | uncertain significance | LZTR1-related schwannomatosis | 2024-03-22 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV005038299 | SCV005656757 | uncertain significance | Noonan syndrome 2; LZTR1-related schwannomatosis; Noonan syndrome 10 | 2024-06-17 | criteria provided, single submitter | clinical testing |