Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001904481 | SCV002123071 | uncertain significance | not provided | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 766 of the LZTR1 protein (p.Met766Val). This variant is present in population databases (rs766793703, 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: 1359663). 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. |
| Ambry Genetics | RCV002449488 | SCV002734810 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-01-05 | criteria provided, single submitter | clinical testing | The p.M766V variant (also known as c.2296A>G), located in coding exon 19 of the LZTR1 gene, results from an A to G substitution at nucleotide position 2296. The methionine at codon 766 is replaced by valine, 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. |
| Baylor Genetics | RCV003470965 | SCV004191258 | uncertain significance | Schwannomatosis 2 | 2023-09-19 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001904481 | SCV005375956 | uncertain significance | not provided | 2023-11-29 | 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; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown; Has not been previously published as pathogenic or benign to our knowledge |