Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics, |
RCV002225193 | SCV002503740 | uncertain significance | LZTR1-related schwannomatosis | 2020-05-28 | criteria provided, single submitter | clinical testing | This sequence change is predicted to replace proline with leucine at codon 308 of the LZTR1 protein (p.Pro308Leu). The proline residue is highly conserved (100 vertebrates, UCSC), and is located in the Kelch 5 repeat. There is a moderate physicochemical difference between proline and leucine. The variant is absent in a large population cohort (PM2; gnomAD v2.1), and has not been reported in the relevant medical literature or databases. Multiple lines of computational evidence predict a deleterious effect for the missense substitution (PP3; 5/7 algorithms). Based on the classification scheme RMH ACMG Guidelines v1.2.1, this variant is classified as VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2, PP3. |
Ambry Genetics | RCV002373052 | SCV002687943 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-06-20 | criteria provided, single submitter | clinical testing | The p.P308L variant (also known as c.923C>T), located in coding exon 9 of the LZTR1 gene, results from a C to T substitution at nucleotide position 923. The proline at codon 308 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. 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. |