Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV003216363 | SCV003911681 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-12-05 | criteria provided, single submitter | clinical testing | The c.1480delA pathogenic mutation, located in coding exon 14 of the LZTR1 gene, results from a deletion of one nucleotide at nucleotide position 1480, causing a translational frameshift with a predicted alternate stop codon (p.R494Gfs*62). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on the supporting evidence, this variant is 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; however, the association of this alteration with autosomal dominant Noonan syndrome is unlikely. |