Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001665466 | SCV001872945 | uncertain significance | not provided | 2021-03-23 | criteria provided, single submitter | clinical testing | Intronic +5 splice site variant in a gene for which loss-of-function is a known mechanism of disease, and both splice predictors and evolutionary conservation support a deleterious effect, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Not observed at a significant frequency in large population cohorts (Lek 2016); Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002425020 | SCV002743254 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-01-12 | criteria provided, single submitter | clinical testing | The c.263+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 2 in the LZTR1 gene. 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 and may result in the creation or strengthening of a novel splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001665466 | SCV003486347 | uncertain significance | not provided | 2023-12-27 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 2 of the LZTR1 gene. It does not directly change the encoded amino acid sequence of the LZTR1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with LZTR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1254541). Variants that disrupt 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. 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. |
| Baylor Genetics | RCV004571068 | SCV005060668 | uncertain significance | Schwannomatosis 2 | 2024-01-04 | criteria provided, single submitter | clinical testing |