Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001345621 | SCV001539752 | uncertain significance | not provided | 2020-09-13 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with LZTR1-related conditions. This sequence change replaces histidine with glutamine at codon 540 of the LZTR1 protein (p.His540Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV002404810 | SCV002708041 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-10-12 | criteria provided, single submitter | clinical testing | The p.H540Q variant (also known as c.1620T>A), located in coding exon 15 of the LZTR1 gene, results from a T to A substitution at nucleotide position 1620. The histidine at codon 540 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Baylor Genetics | RCV004570834 | SCV005060620 | uncertain significance | Schwannomatosis 2 | 2024-03-03 | criteria provided, single submitter | clinical testing |