ClinVar Miner

Submissions for variant NM_006912.6(RIT1):c.244T>C (p.Phe82Leu) (rs869025194)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000254958 SCV000322581 pathogenic not provided 2017-08-14 criteria provided, single submitter clinical testing The F82L variant in the RIT1 gene has been published previously in association with a disorder in the RASopathy spectrum (Cavé et al., 2016). Additionally, another nucleotide change, c.246 T>G, leading to the same amino acid substitution (F82L) has also been associated with RASopathy related disorders (Aoki et al., 2013). The F82L variant is not observed in large population cohorts (Lek et al., 2016). This substitution occurs at a position within the critical Switch II region (Cavé et al., 2016) that is conserved across species. Missense variants in the same codon (F82V) and in nearby residues (A77P, E81G, T83P) have been reported in the Human Gene Mutation Database in association with Noonan syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. Other variants in the same codon (F82V/C) have also been observed in patients referred for RASopathy spectrum disorders at GeneDx. Therefore, we consider the F82L variant to be pathogenic.
Service de Génétique Moléculaire,Hôpital Robert Debré RCV000207346 SCV000211881 pathogenic Noonan syndrome no assertion criteria provided clinical testing

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