Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clinical Genomics Laboratory, |
RCV003456324 | SCV004177029 | uncertain significance | Noonan syndrome | 2023-09-13 | criteria provided, single submitter | clinical testing | The LZTR1 c.1996T>G (p.Phe666Val) variant was identified at near heterozygous allelic fraction and, to our knowledge, it has not been reported in the medical literature. This variant is absent from the general population (gnomAD v3.1.2), indicating it is not a common variant. Computational predictors indicate that the variant is damaging, evidence that correlates with impact to 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. |
| Labcorp Genetics |
RCV003669424 | SCV004384860 | uncertain significance | not provided | 2024-08-29 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 666 of the LZTR1 protein (p.Phe666Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LZTR1-related conditions. 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. |