Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001264608 | SCV001442840 | uncertain significance | not specified | 2020-10-26 | criteria provided, single submitter | clinical testing | Variant summary: LZTR1 c.2134G>C (p.Glu712Gln) results in a conservative amino acid change located in the BTB/POZ domain (IPR000210) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251212 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2134G>C in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Labcorp Genetics |
RCV001880083 | SCV002204610 | uncertain significance | not provided | 2023-04-29 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 984527). This variant has not been reported in the literature in individuals affected with LZTR1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 712 of the LZTR1 protein (p.Glu712Gln). |
| Ambry Genetics | RCV002418868 | SCV002731074 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-04-29 | criteria provided, single submitter | clinical testing | The p.E712Q variant (also known as c.2134G>C), located in coding exon 18 of the LZTR1 gene, results from a G to C substitution at nucleotide position 2134. The glutamic acid at codon 712 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003469495 | SCV004191285 | uncertain significance | Schwannomatosis 2 | 2024-03-22 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001880083 | SCV005379699 | uncertain significance | not provided | 2023-11-26 | 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 |