ClinVar Miner

Submissions for variant NM_006912.6(RIT1):c.335G>A (p.Arg112His)

gnomAD frequency: 0.00001  dbSNP: rs1396631322
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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 RCV002963000 SCV003289429 uncertain significance Noonan syndrome 8 2023-12-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 112 of the RIT1 protein (p.Arg112His). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 2074736). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RIT1 protein 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 RCV004065065 SCV003605132 uncertain significance Cardiovascular phenotype 2022-02-15 criteria provided, single submitter clinical testing The c.335G>A (p.R112H) alteration is located in exon 5 (coding exon 4) of the RIT1 gene. This alteration results from a G to A substitution at nucleotide position 335, causing the arginine (R) at amino acid position 112 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV002963000 SCV004050458 uncertain significance Noonan syndrome 8 2023-04-11 criteria provided, single submitter clinical testing

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