ClinVar Miner

Submissions for variant NM_006912.6(RIT1):c.546A>G (p.Ile182Met)

dbSNP: rs1673291260
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001300610 SCV001489756 uncertain significance Noonan syndrome 8 2017-12-05 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with methionine at codon 182 of the RIT1 protein (p.Ile182Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RIT1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV002281180 SCV002569736 uncertain significance not provided 2022-02-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genome-Nilou Lab RCV001300610 SCV004050435 uncertain significance Noonan syndrome 8 2023-04-11 criteria provided, single submitter clinical testing

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