Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001364081 | SCV001560213 | uncertain significance | not provided | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 444 of the LZTR1 protein (p.Asp444Asn). This variant is present in population databases (rs775051211, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of LZTR1-related disease (PMID: 32004086). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1055416). 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 | RCV002384517 | SCV002692916 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-04-06 | criteria provided, single submitter | clinical testing | The p.D444N variant (also known as c.1330G>A), located in coding exon 12 of the LZTR1 gene, results from a G to A substitution at nucleotide position 1330. The aspartic acid at codon 444 is replaced by asparagine, an amino acid with highly similar properties. It has also been reported in trans with another LZTR1 variant, p.A465V, in two siblings, who had phenotypes consistent with Noonan syndrome (Jenkins J et al. Circ Genom Precis Med, 2020 04;13:e002690). 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. |
| Revvity Omics, |
RCV001364081 | SCV003815329 | uncertain significance | not provided | 2020-08-18 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003469600 | SCV004191262 | uncertain significance | Schwannomatosis 2 | 2024-01-26 | criteria provided, single submitter | clinical testing | |
| Center for Genomic Medicine, |
RCV003469600 | SCV004810270 | uncertain significance | Schwannomatosis 2 | 2024-04-04 | criteria provided, single submitter | clinical testing |