ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.3821C>G (p.Pro1274Arg)

gnomAD frequency: 0.00002  dbSNP: rs886041565
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000303886 SCV000330242 uncertain significance not provided 2016-02-17 criteria provided, single submitter clinical testing The P1274R variant has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P1274R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species. Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. No missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with Noonan syndrome (Stenson et al., 2014).
Labcorp Genetics (formerly Invitae), Labcorp RCV001064842 SCV001229769 uncertain significance RASopathy 2019-12-19 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 1274 of the SOS1 protein (p.Pro1274Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). 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. 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: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SOS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 280339).
Genome-Nilou Lab RCV002467704 SCV002763196 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002467703 SCV002763197 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing

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