ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.1318C>T (p.Arg440Cys)

gnomAD frequency: 0.00004  dbSNP: rs776696572
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
GeneDx RCV002034791 SCV002107210 uncertain significance not provided 2024-04-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV002034791 SCV002194294 uncertain significance not provided 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 440 of the LZTR1 protein (p.Arg440Cys). This variant is present in population databases (rs776696572, gnomAD 0.003%). 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: 1344920). 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.
Ambry Genetics RCV002386585 SCV002691733 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-09-28 criteria provided, single submitter clinical testing The p.R440C variant (also known as c.1318C>T), located in coding exon 12 of the LZTR1 gene, results from a C to T substitution at nucleotide position 1318. The arginine at codon 440 is replaced by cysteine, an amino acid with highly dissimilar 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 RCV004571124 SCV005060609 uncertain significance Schwannomatosis 2 2024-03-12 criteria provided, single submitter clinical testing

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.