Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002383315 | SCV002690210 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-12-18 | criteria provided, single submitter | clinical testing | The c.1354-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 13 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 acceptor site and may 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 one amino acid; however, the exact functional impact of the deleted amino acid is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Revvity Omics, |
RCV003146555 | SCV003833596 | likely pathogenic | not provided | 2022-08-12 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003465717 | SCV004193700 | uncertain significance | Schwannomatosis 2 | 2024-01-30 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003146555 | SCV004275311 | likely pathogenic | not provided | 2023-11-20 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 12 of the LZTR1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LZTR1 are known to be pathogenic (PMID: 24362817, 25335493, 25480913, 25795793, 29469822, 30368668, 30442762, 30442766, 30481304, 30859559). This variant is present in population databases (rs772714594, gnomAD 0.008%). 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: 1770658). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |