ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.150_151del (p.Val51fs)

dbSNP: rs1194536394
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000627644 SCV000748644 likely pathogenic not provided 2018-05-04 criteria provided, single submitter clinical testing The c.150_151delAG variant in the LZTR1 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It causes a frameshift starting with codon Valine 51, changes this amino acid to an Alanine residue and creates a premature Stop codon at position 26 of the new reading frame, denoted p.Val51AlafsX26. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is not observed in large population cohorts (Lek et al., 2016). In summary, we consider this variant to be likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000627644 SCV003290429 pathogenic not provided 2024-08-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val51Alafs*26) 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 (no rsID available, gnomAD 0.003%). 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: 524146). For these reasons, this variant has been classified as Pathogenic.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV004788043 SCV005400179 pathogenic Noonan syndrome 2 2023-12-20 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with autosomal recessive Noonan syndrome 2 (MIM#605275). Dominant negative is the mechanism suspected for autosomal dominant Noonan syndrome 10 (MIM#616564). (I) 0108 - This gene is associated with both recessive and dominant disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 (1 heterozygote, 0 homozygotes). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. This variant has been classified as pathogenic and likely pathogenic by clinical laboratories in ClinVar. (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.