Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001303802 | SCV001493060 | uncertain significance | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 121 of the LZTR1 protein (p.His121Tyr). This variant is not present in population databases (gnomAD no frequency). 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: 1006717). 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. |
| Ambry Genetics | RCV002460141 | SCV002617970 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-06-29 | criteria provided, single submitter | clinical testing | The p.H121Y variant (also known as c.361C>T), located in coding exon 4 of the LZTR1 gene, results from a C to T substitution at nucleotide position 361. The histidine at codon 121 is replaced by tyrosine, 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Genetics and Molecular Pathology, |
RCV003447586 | SCV004175262 | uncertain significance | Noonan syndrome 2; Noonan syndrome 10 | 2023-06-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001303802 | SCV005396343 | uncertain significance | not provided | 2024-05-10 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |