Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001922521 | SCV002167961 | uncertain significance | not provided | 2021-04-14 | 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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 affects codon 775 of the LZTR1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LZTR1 protein. This variant also falls at the last nucleotide of exon 19, which is part of the consensus splice site for this exon. |
| Juno Genomics, |
RCV004796679 | SCV005417097 | uncertain significance | Noonan syndrome 2; LZTR1-related schwannomatosis; Noonan syndrome 10 | criteria provided, single submitter | clinical testing | PM2_Supporting+PM3+PP3 | |
| Ambry Genetics | RCV004996079 | SCV005616219 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-09-30 | criteria provided, single submitter | clinical testing | The c.2325G>A variant (also known as p.Q775Q) is located in coding exon 19 of the LZTR1 gene. This variant results from a G to A substitution at nucleotide position 2325. This nucleotide substitution does not change the amino acid at codon 775. However, this change occurs in the last base pair of coding exon 19, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Based on the available evidence, the clinical significance of this variant remains unclear. |