Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV002306011 | SCV002599610 | uncertain significance | not provided | 2022-05-05 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002400443 | SCV002707238 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-03-06 | criteria provided, single submitter | clinical testing | The p.V523M variant (also known as c.1567G>A), located in coding exon 14 of the LZTR1 gene, results from a G to A substitution at nucleotide position 1567. The valine at codon 523 is replaced by methionine, an amino acid with highly similar properties. This variant has been identified in the homozygous state in an 8 year-old Turkish patient diagnosed with RASopathy, although specific clinical information on this individual was not provided (Demir S et al. Mol Syndromol, 2022 Feb;13:88-98). This amino acid position is 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 |
RCV002306011 | SCV003295771 | uncertain significance | not provided | 2023-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 523 of the LZTR1 protein (p.Val523Met). This variant is present in population databases (rs762957611, gnomAD 0.002%). This missense change has been observed in individual(s) with clinical features of autosomal recessive LZTR1-related disorders (PMID: 35418823). ClinVar contains an entry for this variant (Variation ID: 1722904). 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. 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 | RCV004572225 | SCV005060616 | uncertain significance | Schwannomatosis 2 | 2024-03-05 | criteria provided, single submitter | clinical testing |