Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000485308 | SCV000574437 | uncertain significance | not provided | 2023-11-16 | 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 | RCV002413342 | SCV002681064 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-10-04 | criteria provided, single submitter | clinical testing | The p.K263R variant (also known as c.788A>G), located in coding exon 8 of the LZTR1 gene, results from an A to G substitution at nucleotide position 788. The lysine at codon 263 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not 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 |
RCV000485308 | SCV003268450 | uncertain significance | not provided | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 263 of the LZTR1 protein (p.Lys263Arg). This variant is present in population databases (rs144573377, gnomAD 0.003%). 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: 424613). 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. |
| Baylor Genetics | RCV003470591 | SCV004193627 | uncertain significance | Schwannomatosis 2 | 2023-06-27 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004586736 | SCV005076232 | uncertain significance | not specified | 2024-04-15 | criteria provided, single submitter | clinical testing | Variant summary: LZTR1 c.788A>G (p.Lys263Arg) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 246938 control chromosomes (gnomAD). 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.788A>G in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 424613). Based on the evidence outlined above, the variant was classified as uncertain significance. |