Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002003920 | SCV002274327 | uncertain significance | not provided | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 636 of the LZTR1 protein (p.Pro636Leu). This variant is present in population databases (rs553579098, gnomAD 0.006%). 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: 1486867). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271712 | SCV002556195 | uncertain significance | not specified | 2022-06-27 | criteria provided, single submitter | clinical testing | Variant summary: LZTR1 c.1907C>T (p.Pro636Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 250072 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.1907C>T in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002407244 | SCV002723728 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-10-27 | criteria provided, single submitter | clinical testing | The p.P636L variant (also known as c.1907C>T), located in coding exon 16 of the LZTR1 gene, results from a C to T substitution at nucleotide position 1907. The proline at codon 636 is replaced by leucine, 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 | RCV004571903 | SCV005060592 | uncertain significance | Schwannomatosis 2 | 2024-03-28 | criteria provided, single submitter | clinical testing |