ClinVar Miner

Submissions for variant NM_006912.6(RIT1):c.326A>G (p.His109Arg)

gnomAD frequency: 0.00001  dbSNP: rs1407666045
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001985744 SCV002244112 uncertain significance Noonan syndrome 8 2024-11-27 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 109 of the RIT1 protein (p.His109Arg). This variant is not present in population databases (gnomAD no frequency). 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: 1462672). 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 RCV002324413 SCV002610875 uncertain significance Cardiovascular phenotype 2024-09-23 criteria provided, single submitter clinical testing The p.H109R variant (also known as c.326A>G), located in coding exon 4 of the RIT1 gene, results from an A to G substitution at nucleotide position 326. The histidine at codon 109 is replaced by arginine, 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 RCV001985744 SCV004050460 uncertain significance Noonan syndrome 8 2023-04-11 criteria provided, single submitter clinical testing
GeneDx RCV004591666 SCV005081356 uncertain significance not provided 2024-05-30 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.