Submissions for variant NM_006767.4(LZTR1):c.309C>A (p.Cys103Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center	RCV004784954	SCV005397230	likely pathogenic	Noonan syndrome 2	2022-08-10	criteria provided, single submitter	clinical testing	This sequence variant is a single nucleotide substitution (C>A) at coding nucleotide 309 in the LZTR1 gene which changes the Cys103 codon into an early termition sigl. As it occurs in exon 3 of 21, this variant is predicted to generate a non-functiol allele through the expression of a truncated protein or a loss of LZTR1 expression due to nonsense-mediated decay. This is a novel variant which has not been reported in clinical genetics databases or observed in the medical literature in individuals with LZTR1-related disease, to our knowledge. This variant is absent from the gnomAD control population dataset (0/~251000 alleles). Given the available information, we consider this variant to be likely pathogenic. ACMG Criteria: PM2, PVS1
Labcorp Genetics (formerly Invitae), Labcorp	RCV005105056	SCV005749959	pathogenic	not provided	2024-12-19	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Cys103*) 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 not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LZTR1-related conditions. For these reasons, this variant has been classified as Pathogenic.