ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.570del (p.Phe190fs)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002347615 SCV002650598 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-03-11 criteria provided, single submitter clinical testing The c.570delT pathogenic mutation, located in coding exon 6 of the LZTR1 gene, results from a deletion of one nucleotide at nucleotide position 570, causing a translational frameshift with a predicted alternate stop codon (p.F190Lfs*10). This variant has been detected in two brothers with schwannomatosis (Smith MJ et al. Neurology, 2015 Jan;84:141-7). In addition to the clinical data presented in the literature, 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.
GeneDx RCV003314728 SCV004014382 pathogenic not provided 2023-01-12 criteria provided, single submitter clinical testing Frameshift 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); This variant is associated with the following publications: (PMID: 25480913)
Invitae RCV003314728 SCV004298836 pathogenic not provided 2023-11-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe190Leufs*10) 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 (rs760932744, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with schwannomatosis (PMID: 25480913). ClinVar contains an entry for this variant (Variation ID: 1749215). For these reasons, this variant has been classified as Pathogenic.

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