ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.1319G>A (p.Arg440His)

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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 RCV002385631 SCV002691744 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2023-03-02 criteria provided, single submitter clinical testing The p.R440H variant (also known as c.1319G>A), located in coding exon 12 of the LZTR1 gene, results from a G to A substitution at nucleotide position 1319. The arginine at codon 440 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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 RCV004572402 SCV005060710 uncertain significance LZTR1-related schwannomatosis 2023-11-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005097436 SCV005814063 uncertain significance not provided 2024-10-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 440 of the LZTR1 protein (p.Arg440His). This variant is present in population databases (rs764415634, 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: 1769848). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt LZTR1 protein function with a negative predictive value of 80%. 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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