Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Revvity Omics, |
RCV001782411 | SCV002022740 | likely pathogenic | not provided | 2020-09-23 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001782411 | SCV002219498 | pathogenic | not provided | 2021-03-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln705*) in the LZTR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LZTR1 are known to be pathogenic (PMID: 24362817, 25335493, 25480913, 29469822, 30442762, 30859559). This variant is present in population databases (rs778396468, ExAC 0.006%). This variant has not been reported in the literature in individuals with LZTR1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV004996006 | SCV005616195 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-08-26 | criteria provided, single submitter | clinical testing | The p.Q705* pathogenic mutation (also known as c.2113C>T), located in coding exon 18 of the LZTR1 gene, results from a C to T substitution at nucleotide position 2113. This changes the amino acid from a glutamine to a stop codon within coding exon 18. 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. |