ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.1354-5T>A

gnomAD frequency: 0.00001  dbSNP: rs368421766
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001825092 SCV002074287 uncertain significance not specified 2022-01-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001869835 SCV002313263 uncertain significance not provided 2024-12-30 criteria provided, single submitter clinical testing This sequence change falls in intron 12 of the LZTR1 gene. It does not directly change the encoded amino acid sequence of the LZTR1 protein. This variant is present in population databases (rs368421766, gnomAD 0.007%). 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: 1339704). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002386581 SCV002693123 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-09-25 criteria provided, single submitter clinical testing The c.1354-5T>A intronic variant results from a T to A substitution 5 nucleotides upstream from coding exon 13 in the LZTR1 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive, and direct evidence is insufficient at this time (Ambry internal data). Based on the available evidence, the clinical significance of this variant remains unclear.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003154200 SCV003843159 uncertain significance Noonan syndrome 10 2022-11-16 criteria provided, single submitter clinical testing The LZTR1 c.1354-5T>A intronic change results from a T to A substitution at the -5 position of intron 12 of the LZTR1 gene. Algorithms that predict the impact of sequence changes on splicing indicate that this change may result in loss of the native acceptor site at c.1354 and activation of a cryptic acceptor site, however RNA data is not available to confirm this prediction. This variant has a maximum subpopulation frequency of 0.0064% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). To our knowledge, this variant has not been reported in individuals with Noonan syndrome or Schwannomatosis. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

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