ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.848G>A (p.Arg283Gln) (rs1223430276)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000681082 SCV000808536 likely pathogenic not provided 2019-05-07 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30368668, 33258288)
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV000761304 SCV000891281 likely pathogenic Noonan syndrome 10 2018-11-21 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001269090 SCV001448329 uncertain significance not specified 2020-11-16 criteria provided, single submitter clinical testing Variant summary: LZTR1 c.848G>A (p.Arg283Gln) results in a conservative amino acid change located in the Kelch repeat type 1 domain (IPR006652) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 230510 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.848G>A has been reported in the literature as a de novo mutation in an individual affected with Noonan Syndrome (Umeki_2019). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (Umeki_2019). Two ClinVar submitter (evaluation after 2014) cite the variant as uncertain significance or likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance.
Baylor Genetics RCV000761304 SCV001526201 likely pathogenic Noonan syndrome 10 2018-03-19 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Clinical Genetics,Academic Medical Center RCV000681082 SCV001917340 likely pathogenic not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000681082 SCV001956355 pathogenic not provided no assertion criteria provided clinical testing

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