Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002351590 | SCV002652732 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-05-27 | criteria provided, single submitter | clinical testing | The p.Y183* variant (also known as c.549C>G), located in coding exon 6 of the LZTR1 gene, results from a C to G substitution at nucleotide position 549. This changes the amino acid from a tyrosine to a stop codon within coding exon 6. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on the supporting evidence, this variant is pathogenic for an increased risk of nerve sheath tumors 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. |
| Invitae | RCV003718522 | SCV004508275 | pathogenic | not provided | 2023-12-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr183*) 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). This variant is not present in population databases (gnomAD no frequency). 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: 1747900). For these reasons, this variant has been classified as Pathogenic. |