Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002432437 | SCV002730429 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-08-24 | criteria provided, single submitter | clinical testing | The c.214dupA pathogenic mutation, located in coding exon 2 of the LZTR1 gene, results from a duplication of A at nucleotide position 214, causing a translational frameshift with a predicted alternate stop codon (p.T72Nfs*6). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |