ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.1798A>C (p.Ile600Leu)

dbSNP: rs373139450
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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 RCV000698499 SCV000827166 uncertain significance RASopathy 2019-06-25 criteria provided, single submitter clinical testing 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 disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with leucine at codon 600 of the SOS1 protein (p.Ile600Leu). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and leucine. 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.
GeneDx RCV003228981 SCV003926296 uncertain significance not provided 2022-11-17 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29493581)
Ambry Genetics RCV004993967 SCV005506105 uncertain significance Cardiovascular phenotype 2024-10-19 criteria provided, single submitter clinical testing The p.I600L variant (also known as c.1798A>C), located in coding exon 10 of the SOS1 gene, results from an A to C substitution at nucleotide position 1798. The isoleucine at codon 600 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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