Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001944011 | SCV002216642 | uncertain significance | not provided | 2023-08-20 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 1432646). This variant has not been reported in the literature in individuals affected with LZTR1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 813 of the LZTR1 protein (p.Ser813Gly). |
| Ambry Genetics | RCV002458835 | SCV002737228 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-06-28 | criteria provided, single submitter | clinical testing | The p.S813G variant (also known as c.2437A>G), located in coding exon 21 of the LZTR1 gene, results from an A to G substitution at nucleotide position 2437. The serine at codon 813 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly 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. |
| Baylor Genetics | RCV003471079 | SCV004193663 | uncertain significance | Schwannomatosis 2 | 2024-02-23 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004538647 | SCV004714727 | uncertain significance | LZTR1-related disorder | 2024-02-17 | no assertion criteria provided | clinical testing | The LZTR1 c.2437A>G variant is predicted to result in the amino acid substitution p.Ser813Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD and has been interpreted in ClinVar as uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/1432646/). Of note, a different variant impacting the same amino acid residue (p.Ser813Ile) has been documented in an individual with schwannomatosis (Subject S1, Piotrowski et al. 2014. PubMed ID: 24362817). At this time, the clinical significance of the c.2437A>G (p.Ser813Gly) variant is uncertain due to the absence of conclusive functional and genetic evidence. |