Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001810660 | SCV001477588 | uncertain significance | not provided | 2020-03-03 | criteria provided, single submitter | clinical testing | The LZTR1 c.2407-18G>A variant (rs542841506), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found in the general population with an overall allele frequency of 0.015% (42/280862 alleles) in the Genome Aggregation Database. This is an intronic variant in a weakly conserved nucleotide, but computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating a novel cryptic acceptor splice site. However, without functional studies the effect on splicing is unknown. Loss of function variants in LZTR1 are associated with autosomal recessive Noonan syndrome and schwannomatosis (Motta 2019, Pagnamenta 2019). Due to limited information, the clinical significance of the c.2407-18G>A variant is uncertain at this time. References: Motta M et al. Dominant Noonan syndrome-causing LZTR1 mutations specifically affect the Kelch domain substrate-recognition surface and enhance RAS-MAPK signaling. Hum Mol Genet. 2019 Mar 15;28(6):1007-1022. Pagnamenta AT et al. Delineation of dominant and recessive forms of LZTR1-associated Noonan syndrome. Clin Genet. 2019 Jun;95(6):693-703. |
Labcorp Genetics |
RCV001810660 | SCV002354539 | likely benign | not provided | 2025-01-23 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003469504 | SCV004193674 | uncertain significance | LZTR1-related schwannomatosis | 2023-04-16 | criteria provided, single submitter | clinical testing |