Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002457891 | SCV002735943 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-03-22 | criteria provided, single submitter | clinical testing | The p.H794Y variant (also known as c.2380C>T), located in coding exon 20 of the LZTR1 gene, results from a C to T substitution at nucleotide position 2380. The histidine at codon 794 is replaced by tyrosine, an amino acid with similar properties. This alteration was paternally inherited in an individual with intellectual disability and facial dysmorphology who was also found to have a 46,XY,t(9;18)(p13;q12.2) as well as a small gain on chromosome 4 in a non-disease associated region (Nizon M et al. Genet Med, 2019 12;21:2713-2722). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003465755 | SCV004193621 | uncertain significance | Schwannomatosis 2 | 2023-07-10 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003720627 | SCV004510513 | uncertain significance | not provided | 2023-12-16 | 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 794 of the LZTR1 protein (p.His794Tyr). 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: 1790438). 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. |