ClinVar Miner

Submissions for variant NM_005343.4(HRAS):c.304C>T (p.Arg102Trp)

gnomAD frequency: 0.00001  dbSNP: rs1057517913
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414564 SCV000491050 uncertain significance not specified 2015-08-28 criteria provided, single submitter clinical testing The R102W variant has not been published as a pathogenic or been reported as a benign to our knowledge. The R102W 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. Additionally, the R102W 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. Moreover, this substitution occurs at a position conserved across species. Consequently, in silico analysis predicts this variant is probably damaging to the protein structure/function. However, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with Costello syndrome (Stenson et al., 2014).
Labcorp Genetics (formerly Invitae), Labcorp RCV001369972 SCV001566431 uncertain significance Costello syndrome 2023-08-10 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 102 of the HRAS protein (p.Arg102Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HRAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 372666). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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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