ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.1686G>T (p.Glu562Asp)

dbSNP: rs199778219
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002040210 SCV002291199 uncertain significance RASopathy 2022-08-15 criteria provided, single submitter clinical testing 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) performed at Invitae indicates that this missense variant is expected to disrupt SOS1 protein function. ClinVar contains an entry for this variant (Variation ID: 1499402). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 562 of the SOS1 protein (p.Glu562Asp).
GeneDx RCV002221697 SCV002499030 uncertain significance not provided 2024-07-24 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter 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)
Ambry Genetics RCV002407270 SCV002715877 uncertain significance Cardiovascular phenotype 2022-01-26 criteria provided, single submitter clinical testing The p.E562D variant (also known as c.1686G>T), located in coding exon 10 of the SOS1 gene, results from a G to T substitution at nucleotide position 1686. The glutamic acid at codon 562 is replaced by aspartic acid, an amino acid with highly 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.
Genome-Nilou Lab RCV002468379 SCV002763383 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002468378 SCV002763384 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing

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