ClinVar Miner

Submissions for variant NM_006912.6(RIT1):c.635G>A (p.Arg212Gln)

gnomAD frequency: 0.00004  dbSNP: rs764347644
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001813688 SCV002060856 uncertain significance Noonan syndrome and Noonan-related syndrome 2020-09-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001869619 SCV002198136 uncertain significance Noonan syndrome 8 2025-01-20 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 212 of the RIT1 protein (p.Arg212Gln). This variant is present in population databases (rs764347644, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RIT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1334273). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt RIT1 function with a negative predictive value of 95%. 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.
Ambry Genetics RCV002361067 SCV002658032 uncertain significance Cardiovascular phenotype 2022-07-29 criteria provided, single submitter clinical testing The p.R212Q variant (also known as c.635G>A), located in coding exon 5 of the RIT1 gene, results from a G to A substitution at nucleotide position 635. The arginine at codon 212 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV001869619 SCV004050428 uncertain significance Noonan syndrome 8 2023-04-11 criteria provided, single submitter clinical testing

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