Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center For Human Genetics And Laboratory Diagnostics, |
RCV000523227 | SCV000616599 | uncertain significance | Noonan syndrome 10 | 2017-04-11 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001851476 | SCV002109370 | uncertain significance | not provided | 2025-01-01 | 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 661 of the LZTR1 protein (p.Gly661Glu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 448963). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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 | RCV002420304 | SCV002717875 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-10-05 | criteria provided, single submitter | clinical testing | The p.G661E variant (also known as c.1982G>A), located in coding exon 17 of the LZTR1 gene, results from a G to A substitution at nucleotide position 1982. The glycine at codon 661 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 | RCV003470644 | SCV004191209 | uncertain significance | LZTR1-related schwannomatosis | 2024-01-27 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004701590 | SCV005205092 | uncertain significance | not specified | 2024-06-06 | criteria provided, single submitter | clinical testing | Variant summary: LZTR1 c.1982G>A (p.Gly661Glu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.7e-05 in 1613492 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in LZTR1 causing autosomal recessive Noonan Syndrome 2 (1.7e-05 vs 0.0032), allowing no conclusion about variant significance for LZTR1-related conditions. To our knowledge, no occurrence of c.1982G>A in individuals affected with LZTR1-related conditions and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 448963). Based on the evidence outlined above, the variant was classified as uncertain significance. |