ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.423T>G (p.Tyr141Ter)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002328204 SCV002632857 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-12-04 criteria provided, single submitter clinical testing The p.Y141* pathogenic mutation (also known as c.423T>G), located in coding exon 5 of the LZTR1 gene, results from a T to G substitution at nucleotide position 423. This changes the amino acid from a tyrosine to a stop codon within coding exon 5. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003094603 SCV003457204 pathogenic not provided 2023-08-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1738993). This variant has not been reported in the literature in individuals affected with LZTR1-related conditions. This variant is present in population databases (rs141357465, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Tyr141*) 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).
Fulgent Genetics, Fulgent Genetics RCV005025798 SCV005656725 likely pathogenic Noonan syndrome 2; LZTR1-related schwannomatosis; Noonan syndrome 10 2024-05-23 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.