ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.1294T>A (p.Trp432Arg)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002293901 SCV002586887 pathogenic not provided 2022-10-17 criteria provided, single submitter clinical testing Missense variants in this gene are often considered pathogenic (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31219622, 34184824, 29493581, 20648242, 17143282, 21387466, 12628188)
Labcorp Genetics (formerly Invitae), Labcorp RCV003655354 SCV004536949 pathogenic RASopathy 2023-03-19 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 432 of the SOS1 protein (p.Trp432Arg). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SOS1 protein function. ClinVar contains an entry for this variant (Variation ID: 1712183). This missense change has been observed in individual(s) with clinical features of Noonan syndrome (PMID: 17143282, 17586837, 19438935, 21387466, 22465605, 31219622, 34184824). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic.

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