ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.1333A>G (p.Ile445Val)

dbSNP: rs2124537533
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001760849 SCV001991480 uncertain significance not provided 2019-07-24 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001861114 SCV002281593 uncertain significance RASopathy 2021-04-19 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SOS1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with valine at codon 445 of the SOS1 protein (p.Ile445Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine.
Genome-Nilou Lab RCV002468301 SCV002763423 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002468300 SCV002763424 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing

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