ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.499A>C (p.Ile167Leu)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002342980 SCV002642314 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-11-04 criteria provided, single submitter clinical testing The p.I167L variant (also known as c.499A>C), located in coding exon 5 of the LZTR1 gene, results from an A to C substitution at nucleotide position 499. The isoleucine at codon 167 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003471345 SCV004191308 uncertain significance Schwannomatosis 2 2023-08-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003688974 SCV004452708 uncertain significance not provided 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 167 of the LZTR1 protein (p.Ile167Leu). This variant is present in population databases (rs778265576, gnomAD 0.004%). 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: 1744630). 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%. 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.
PreventionGenetics, part of Exact Sciences RCV004736158 SCV005365652 uncertain significance LZTR1-related disorder 2024-04-29 no assertion criteria provided clinical testing The LZTR1 c.499A>C variant is predicted to result in the amino acid substitution p.Ile167Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0044% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.