ClinVar Miner

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

dbSNP: rs767445373
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Total submissions: 4
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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 ( In ClinVar, this variant is classified as pathogenic ( 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

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