ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.1564A>C (p.Asn522His)

gnomAD frequency: 0.00001  dbSNP: rs761094509
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000217384 SCV000272446 uncertain significance not specified 2016-01-07 criteria provided, single submitter clinical testing The p.Asn522His variant in SOS1 has not been previously reported in individuals with a RASopathy disorder, but has been identified in 3/66294 of European chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs761094509). Computational prediction tools and conservation analysis su ggest that this variant may impact the protein, though this information is not p redictive enough to determine pathogenicity. In summary, the clinical significan ce of the p.Asn522His variant is uncertain
Fulgent Genetics, Fulgent Genetics RCV000764406 SCV000895463 uncertain significance Fibromatosis, gingival, 1; Noonan syndrome 4 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001365177 SCV001561435 uncertain significance RASopathy 2020-05-27 criteria provided, single submitter clinical testing 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: 229262). This variant is present in population databases (rs761094509, ExAC 0.005%). This sequence change replaces asparagine with histidine at codon 522 of the SOS1 protein (p.Asn522His). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and histidine.
Genome-Nilou Lab RCV002467685 SCV002763403 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002467684 SCV002763404 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing

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