Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004995495 | SCV005617342 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-07-30 | criteria provided, single submitter | clinical testing | The c.1886delT pathogenic mutation, located in coding exon 16 of the LZTR1 gene, results from a deletion of one nucleotide at nucleotide position 1886, causing a translational frameshift with a predicted alternate stop codon (p.V629Gfs*23). Loss-of-function variants in LZTR1 are related to an increased risk for schwannomas and autosomal recessive Noonan syndrome; however, such associations with autosomal dominant Noonan syndrome have not been observed (Piotrowski A et al. Nat Genet. 2014 Feb;46:182-7; Yamamoto GL et al. J Med Genet. 2015 Jun;52:413-21; Johnston JJ et al. Genet Med. 2018 10;20:1175-1185). 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. |