Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001386885 | SCV001587283 | pathogenic | not provided | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln577*) 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, 25795793, 29469822, 30368668, 30442762, 30442766, 30481304, 30859559). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with LZTR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1073780). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001386885 | SCV002072846 | likely pathogenic | not provided | 2023-11-08 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30442766, 30481304, 24362817, 30859559, 29469822, 25795793, 25480913, 25335493, 30442762) |
| Ambry Genetics | RCV002404902 | SCV002712518 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-10-04 | criteria provided, single submitter | clinical testing | The p.Q577* pathogenic mutation (also known as c.1729C>T), located in coding exon 15 of the LZTR1 gene, results from a C to T substitution at nucleotide position 1729. This changes the amino acid from a glutamine to a stop codon within coding exon 15. 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. |