Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001914558 | SCV002142933 | uncertain significance | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 169 of the LZTR1 protein (p.Gly169Glu). This variant is present in population databases (rs751873839, gnomAD 0.02%). 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: 1378213). 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 | RCV002334791 | SCV002642881 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-12-26 | criteria provided, single submitter | clinical testing | The p.G169E variant (also known as c.506G>A), located in coding exon 5 of the LZTR1 gene, results from a G to A substitution at nucleotide position 506. The glycine at codon 169 is replaced by glutamic acid, an amino acid with 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 | RCV003470985 | SCV004191232 | uncertain significance | Schwannomatosis 2 | 2023-10-09 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004734313 | SCV005359535 | uncertain significance | LZTR1-related disorder | 2024-09-24 | no assertion criteria provided | clinical testing | The LZTR1 c.506G>A variant is predicted to result in the amino acid substitution p.Gly169Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.020% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |