Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Blueprint Genetics | RCV000788490 | SCV000927629 | uncertain significance | not provided | 2018-04-14 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002325490 | SCV002627260 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2020-11-27 | criteria provided, single submitter | clinical testing | The p.Y136H variant (also known as c.406T>C), located in coding exon 5 of the LZTR1 gene, results from a T to C substitution at nucleotide position 406. The tyrosine at codon 136 is replaced by histidine, an amino acid with similar properties. This variant has been identified de novo in a patient with some features suggestive of Noonan syndrome (Pagnamenta AT et al. Clin Genet, 2019 06;95:693-703). 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. |
| Labcorp Genetics |
RCV000788490 | SCV003787186 | pathogenic | not provided | 2022-09-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Tyr136 amino acid residue in LZTR1. Other variant(s) that disrupt this residue have been observed in individuals with LZTR1-related conditions (PMID: 30859559), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 636611). This missense change has been observed in individual(s) with autosomal dominant LZTR1-related conditions (PMID: 30859559). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 136 of the LZTR1 protein (p.Tyr136His). |