Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001933719 | SCV002203044 | uncertain significance | not provided | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 496 of the LZTR1 protein (p.Ala496Tyr). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 1427466). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 | RCV002388868 | SCV002702635 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-02-23 | criteria provided, single submitter | clinical testing | The c.1486_1487delGCinsTA variant (also known as p.A496Y), located in coding exon 14 of the LZTR1 gene, results from an in-frame deletion of GC and insertion of TA at nucleotide positions 1486 to 1487. This results in the substitution of the alanine residue for a tyrosine residue at codon 496, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Baylor Genetics | RCV003464249 | SCV004193634 | uncertain significance | Schwannomatosis 2 | 2023-06-23 | criteria provided, single submitter | clinical testing |