Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001324216 | SCV001515161 | uncertain significance | not provided | 2025-02-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 505 of the LZTR1 protein (p.Arg505Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1024076). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002242276 | SCV002511756 | uncertain significance | not specified | 2024-08-02 | criteria provided, single submitter | clinical testing | Variant summary: LZTR1 c.1513C>T (p.Arg505Trp) results in a non-conservative amino acid change located in the BTB/POZ domain (IPR000210) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.8e-05 in 217222 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1513C>T has been reported in the literature in individuals affected with Noonan Syndrome. These report(s) do not provide unequivocal conclusions about association of the variant with Noonan Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 1024076). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002395712 | SCV002709800 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-12-07 | criteria provided, single submitter | clinical testing | The p.R505W variant (also known as c.1513C>T), located in coding exon 14 of the LZTR1 gene, results from a C to T substitution at nucleotide position 1513. The arginine at codon 505 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is poorly 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. |
| Gene |
RCV001324216 | SCV004014184 | uncertain significance | not provided | 2024-02-25 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with an unexplained cardiac arrest in the published literature (PMID: 35352813); This variant is associated with the following publications: (PMID: 35352813) |
| Baylor Genetics | RCV003469553 | SCV004193643 | uncertain significance | LZTR1-related schwannomatosis | 2024-02-25 | criteria provided, single submitter | clinical testing |