ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.1946C>T (p.Thr649Ile)

dbSNP: rs774401447
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002039940 SCV002113245 uncertain significance not provided 2024-02-01 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 649 of the LZTR1 protein (p.Thr649Ile). This variant is present in population databases (rs774401447, gnomAD 0.0009%). 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: 1352771). 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%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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 RCV002406926 SCV002719325 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-03-07 criteria provided, single submitter clinical testing The p.T649I variant (also known as c.1946C>T), located in coding exon 17 of the LZTR1 gene, results from a C to T substitution at nucleotide position 1946. The threonine at codon 649 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV004571429 SCV005060685 uncertain significance Schwannomatosis 2 2023-12-15 criteria provided, single submitter clinical testing

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