ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.890_891del (p.Tyr297fs)

dbSNP: rs767445373
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001386716 SCV001587062 pathogenic not provided 2024-01-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr297Cysfs*18) 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 present in population databases (rs767445373, gnomAD 0.006%). 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: 1073645). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002377574 SCV002687462 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2023-08-03 criteria provided, single submitter clinical testing The c.890_891delAT pathogenic mutation, located in coding exon 9 of the LZTR1 gene, results from a deletion of two nucleotides at nucleotide positions 890 to 891, causing a translational frameshift with a predicted alternate stop codon (p.Y297Cfs*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.
PreventionGenetics, part of Exact Sciences RCV004528498 SCV004105709 pathogenic LZTR1-related disorder 2023-04-13 criteria provided, single submitter clinical testing The LZTR1 c.890_891delAT variant is predicted to result in a frameshift and premature protein termination (p.Tyr297Cysfs*18). This variant has not been reported in the literature. This variant is reported in 0.0058% of alleles in individuals of European (Non-Finnish) descent in gnomAD (https://gnomad.broadinstitute.org/variant/chr22-21346013-CTA-C). In ClinVar, this variant is classified as pathogenic (https://preview.ncbi.nlm.nih.gov/clinvar/variation/1073645/). Frameshift variants in LZTR1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Baylor Genetics RCV003469723 SCV004191831 likely pathogenic Schwannomatosis 2 2024-03-11 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.