Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002381101 | SCV002699528 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-01-17 | criteria provided, single submitter | clinical testing | The p.V460I variant (also known as c.1378G>A), located in coding exon 13 of the LZTR1 gene, results from a G to A substitution at nucleotide position 1378. The valine at codon 460 is replaced by isoleucine, 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. |
| Labcorp Genetics |
RCV003546818 | SCV004268552 | uncertain significance | not provided | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 460 of the LZTR1 protein (p.Val460Ile). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1771223). 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. |
| Baylor Genetics | RCV004572412 | SCV005060674 | uncertain significance | Schwannomatosis 2 | 2023-12-29 | criteria provided, single submitter | clinical testing |