Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001040994 | SCV001204588 | uncertain significance | not provided | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 524 of the LZTR1 protein (p.Leu524Phe). This variant is not present in population databases (gnomAD no frequency). 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: 839278). 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. 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 | RCV002400242 | SCV002704070 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-02-21 | criteria provided, single submitter | clinical testing | The p.L524F variant (also known as c.1570C>T), located in coding exon 14 of the LZTR1 gene, results from a C to T substitution at nucleotide position 1570. The leucine at codon 524 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration has been detected in an individual with a personal history of schwannomas (Ambry internal data). 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. |
Prevention |
RCV004536075 | SCV004113597 | uncertain significance | LZTR1-related disorder | 2023-03-11 | criteria provided, single submitter | clinical testing | The LZTR1 c.1570C>T variant is predicted to result in the amino acid substitution p.Leu524Phe. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. In ClinVar, this variant is interpreted as uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/839278/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Baylor Genetics | RCV004570129 | SCV005060671 | uncertain significance | Schwannomatosis 2 | 2024-01-03 | criteria provided, single submitter | clinical testing |