Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000414560 | SCV000491465 | likely pathogenic | not provided | 2023-05-21 | criteria provided, single submitter | clinical testing | Observed in an individual with autism (Guo et al., 2019); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30504930, 30368668, 30481304, 25795793, 29469822, 30442766, 30859559, 24362817, 30442762, 25335493, 25480913) |
| Invitae | RCV000414560 | SCV001404178 | pathogenic | not provided | 2024-01-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Phe258Leufs*93) in the LZTR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LZTR1 are known to be pathogenic (PMID: 24362817, 25335493, 25480913, 25795793, 29469822, 30368668, 30442762, 30442766, 30481304, 30859559). This variant is present in population databases (rs780267761, gnomAD 0.006%). 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: 372924). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002411278 | SCV002669981 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2020-08-21 | criteria provided, single submitter | clinical testing | The c.774delT pathogenic mutation, located in coding exon 8 of the LZTR1 gene, results from a deletion of one nucleotide at nucleotide position 774, causing a translational frameshift with a predicted alternate stop codon (p.F258Lfs*93). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on the supporting evidence, this variant is expected to be pathogenic for autosomal dominant risk of schwannomatosis and would be expected to cause autosomal recessive Noonan syndrome when present along with a second pathogenic variant on the other allele. |
| Prevention |
RCV003392229 | SCV004118811 | likely pathogenic | LZTR1-related condition | 2023-08-10 | criteria provided, single submitter | clinical testing | The LZTR1 c.774delT variant is predicted to result in a frameshift and premature protein termination (p.Phe258Leufs*93). To our knowledge, this variant has not been reported in an individual LZTR1-related disease. This variant is reported in 0.0062% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/22-21344794-GT-G). Frameshift variants in LZTR1 are expected to be pathogenic for autosomal recessive Noonan syndrome and autosomal dominant susceptibility to schwannomatosis. However, the role of frameshift variants in autosomal dominant Noonan syndrome is uncertain (see below). This variant is interpreted as likely pathogenic. |
| Baylor Genetics | RCV003476002 | SCV004193612 | likely pathogenic | Schwannomatosis 2 | 2023-07-23 | criteria provided, single submitter | clinical testing | |
| University of Washington Center for Mendelian Genomics, |
RCV001291506 | SCV001480011 | association | Autism spectrum disorder | no assertion criteria provided | research |