Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002383490 | SCV002699997 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-12-06 | criteria provided, single submitter | clinical testing | The p.E454* variant (also known as c.1360G>T), located in coding exon 13 of the LZTR1 gene, results from a G to T substitution at nucleotide position 1360. This changes the amino acid from a glutamic acid to a stop codon within coding exon 13. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. 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. |
| Baylor Genetics | RCV004572410 | SCV005060707 | likely pathogenic | LZTR1-related schwannomatosis | 2023-11-22 | criteria provided, single submitter | clinical testing |