ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.305C>G (p.Pro102Arg)

dbSNP: rs1553362937
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000544063 SCV000659142 pathogenic RASopathy 2023-08-17 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 102 of the SOS1 protein (p.Pro102Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Noonan syndrome (PMID: 19953625, 32981126). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 477721). 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. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001591305 SCV001824905 likely pathogenic not provided 2021-04-19 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 32981126, 20461756, 24803665, 19953625)
Genome-Nilou Lab RCV002467898 SCV002763593 likely pathogenic Noonan syndrome 4 criteria provided, single submitter clinical testing

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