Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV003470013 | SCV004191269 | likely pathogenic | LZTR1-related schwannomatosis | 2023-09-09 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004560177 | SCV005047303 | likely pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-05-09 | criteria provided, single submitter | clinical testing | The c.1449+2T>G intronic variant results from a T to G substitution two nucleotides after coding exon 13 in the LZTR1 gene. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNA decay. Although the exact functional effect of the altered amino acid sequence is unknown, the impacted region is critical for protein function (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. Based on the supporting evidence, this variant is likely pathogenic for an increased risk of LZTR1-related schwannomatosis (SWN) and would be expected to cause autosomal recessive Noonan syndrome when present along with a second pathogenic or likely pathogenic variant on the other allele. |