ClinVar Miner

Submissions for variant NM_006270.5(RRAS):c.572G>A (p.Arg191Gln)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000794537 SCV000933951 uncertain significance Noonan syndrome 2018-08-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 191 of the RRAS protein (p.Arg191Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant also falls at the last nucleotide of exon 5 of the RRAS coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs759803129, ExAC 0.002%). This variant has not been reported in the literature in individuals with RRAS-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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