ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.271A>G (p.Met91Val)

dbSNP: rs1135401945
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues RCV000496323 SCV000588139 uncertain significance Noonan syndrome 10 2017-01-25 criteria provided, single submitter clinical testing
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues RCV000522143 SCV000616593 uncertain significance RASopathy 2017-01-25 criteria provided, single submitter clinical testing
Invitae RCV001856992 SCV002313726 uncertain significance not provided 2023-11-14 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 91 of the LZTR1 protein (p.Met91Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant Noonan syndrome (PMID: 34184824). ClinVar contains an entry for this variant (Variation ID: 431371). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LZTR1 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects LZTR1 function (PMID: 30481304). 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.

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