Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001909943 | SCV002186026 | uncertain significance | not provided | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 212 of the LZTR1 protein (p.Leu212Arg). This variant is present in population databases (rs138301732, gnomAD 0.004%). 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: 1408382). 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 | RCV002361215 | SCV002659036 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-01-12 | criteria provided, single submitter | clinical testing | The p.L212R variant (also known as c.635T>G), located in coding exon 7 of the LZTR1 gene, results from a T to G substitution at nucleotide position 635. The leucine at codon 212 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well 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 | RCV004571590 | SCV005060644 | uncertain significance | Schwannomatosis 2 | 2024-02-07 | criteria provided, single submitter | clinical testing |