ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.1691A>G (p.Glu564Gly)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002406160 SCV002710879 uncertain significance Cardiovascular phenotype 2021-10-06 criteria provided, single submitter clinical testing The p.E564G variant (also known as c.1691A>G), located in coding exon 10 of the SOS1 gene, results from an A to G substitution at nucleotide position 1691. The glutamic acid at codon 564 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003322918 SCV004028261 uncertain significance not provided 2023-02-16 criteria provided, single submitter clinical testing 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 (HGMD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29493581)
Labcorp Genetics (formerly Invitae), Labcorp RCV003539449 SCV004284956 uncertain significance RASopathy 2023-05-26 criteria provided, single submitter clinical testing This variant is present in population databases (rs571743548, gnomAD 0.007%). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 564 of the SOS1 protein (p.Glu564Gly). This variant has not been reported in the literature in individuals affected with SOS1-related conditions. 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SOS1 protein function. ClinVar contains an entry for this variant (Variation ID: 1778138).

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