Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002404083 | SCV002713442 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2020-12-07 | criteria provided, single submitter | clinical testing | The p.L594F variant (also known as c.1780C>T), located in coding exon 15 of the LZTR1 gene, results from a C to T substitution at nucleotide position 1780. The leucine at codon 594 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003097241 | SCV003523046 | uncertain significance | not provided | 2023-01-24 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 594 of the LZTR1 protein (p.Leu594Phe). This variant has not been reported in the literature in individuals affected with LZTR1-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 1779985). |
| Gene |
RCV003097241 | SCV003924514 | uncertain significance | not provided | 2022-11-15 | 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 |
| Baylor Genetics | RCV004572439 | SCV005060659 | uncertain significance | Schwannomatosis 2 | 2024-01-22 | criteria provided, single submitter | clinical testing |