ClinVar Miner

Submissions for variant NM_006912.6(RIT1):c.461G>A (p.Arg154Gln)

gnomAD frequency: 0.00001  dbSNP: rs754596127
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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 RCV000808742 SCV000948860 uncertain significance Noonan syndrome 8 2024-07-29 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 154 of the RIT1 protein (p.Arg154Gln). This variant is present in population databases (rs754596127, 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: 653052). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) 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.
GeneDx RCV001571706 SCV001796225 likely benign not provided 2020-10-08 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 653052; Landrum et al., 2016)
Ambry Genetics RCV002332657 SCV002633396 uncertain significance Cardiovascular phenotype 2024-01-08 criteria provided, single submitter clinical testing The p.R154Q variant (also known as c.461G>A), located in coding exon 5 of the RIT1 gene, results from a G to A substitution at nucleotide position 461. The arginine at codon 154 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. 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.

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