Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002049448 | SCV002117349 | uncertain significance | not provided | 2021-09-15 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This variant has not been reported in the literature in individuals with LZTR1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 555 of the LZTR1 protein (p.Leu555Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. |
| Ambry Genetics | RCV002397782 | SCV002706563 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-07-21 | criteria provided, single submitter | clinical testing | The p.L555V variant (also known as c.1663C>G), located in coding exon 15 of the LZTR1 gene, results from a C to G substitution at nucleotide position 1663. The leucine at codon 555 is replaced by valine, an amino acid with highly similar properties. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice acceptor site. RNA studies have demonstrated that this alteration results in a transcript predicted to lead to a protein with an in-frame deletion of 17 amino acid(s) with an accompanying single amino acid insertion; however, the exact functional impact of the altered amino acid(s) is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003464166 | SCV004191280 | uncertain significance | Schwannomatosis 2 | 2023-08-28 | criteria provided, single submitter | clinical testing |