ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.742G>A (p.Gly248Arg) (rs869320686)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413889 SCV000491461 pathogenic not provided 2018-09-11 criteria provided, single submitter clinical testing The G248R variant in the LZTR1 gene has been reported previously in an individual with a clinical diagnosis of Noonan syndrome, as well as in that individual’s affected mother and grandfather (Yamamoto et al., 2015). The G248R variant is not observed in large population cohorts (Lek et al., 2016). The G248R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position within Kelch domain 4 that is conserved across species (UniProt Consortium, 2015). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. This variant has been identified as de novo with confirmed parentage in a patient with a LZTR1-related disorder previously tested at GeneDx. We interpret G248R as a pathogenic variant.
Ambry Genetics RCV000623699 SCV000743074 likely pathogenic Inborn genetic diseases 2017-10-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Fulgent Genetics,Fulgent Genetics RCV000763072 SCV000893582 likely pathogenic Schwannomatosis 2; Noonan syndrome 10 2018-10-31 criteria provided, single submitter clinical testing
Genetics Molecular Biology Lab, Hospital Juan P Garrahan RCV000191027 SCV000920884 pathogenic Noonan syndrome 10 criteria provided, single submitter clinical testing
OMIM RCV000191027 SCV000246007 pathogenic Noonan syndrome 10 2015-06-01 no assertion criteria provided literature only

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