Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000627478 | SCV000748478 | pathogenic | not provided | 2018-03-20 | criteria provided, single submitter | clinical testing | The c.1030delT variant in the LZTR1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1030delT variant causes a frameshift starting with codon Serine 344, changes this amino acid to a Proline residue, and creates a premature Stop codon at position 7 of the new reading frame, denoted p.Ser344ProfsX7. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1030delT variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1030delT as a pathogenic variant. |
Broad Center for Mendelian Genomics, |
RCV001267719 | SCV001445973 | likely pathogenic | Noonan syndrome 2 | 2020-11-16 | criteria provided, single submitter | curation | The heterozygous p.Ser344ProfsTer7 variant in LZTR1 was identified by our study in the compound heterozygous state, along with another pathogenic variant, in 2 siblings with Noonan syndrome 2. The variant has not been previously reported in individuals with Noonan syndrome 2 and was absent from large population studies. This variant has also been reported in ClinVar (Variation ID: 523986) as pathogenic by GeneDx. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 344 and leads to a premature termination codon 7 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the LZTR1 gene is strongly associated to autosomal recessive Noonan syndrome 2. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1_strong, PM2, PM3 (Richards 2015). |