ClinVar Miner

Submissions for variant NM_001354689.3(RAF1):c.505G>C (p.Gly169Arg) (rs886039607)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255759 SCV000322511 likely pathogenic not provided 2018-07-20 criteria provided, single submitter clinical testing The G169R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, the variant has been observed at GeneDx to occur apparently de novo in an affected individual. The G169R variant was not observed in large population cohorts (Lek et al., 2016). The G169R 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 that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000576681 SCV000678225 pathogenic LEOPARD syndrome 2; Noonan syndrome 5 2017-08-01 criteria provided, single submitter clinical testing RAF1 NM_002880.3 exon5 p.Gly169Arg (c.505G>C):This variant has not been reported in the literature and is not present in large control databases. However, this variant is present in ClinVar, reportedly identified de novo by another laboratory (Variation ID:265535). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant classified as likely pathogenic.
Service de Génétique Moléculaire,Hôpital Robert Debré RCV001261029 SCV001438427 likely benign Noonan syndrome no assertion criteria provided clinical testing

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