ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.1988T>C (p.Ile663Thr)

gnomAD frequency: 0.00003  dbSNP: rs1048869073
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001754722 SCV001996299 uncertain significance not provided 2019-10-01 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001882888 SCV002146138 uncertain significance RASopathy 2023-09-26 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 663 of the SOS1 protein (p.Ile663Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SOS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1308834). 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 not expected to disrupt SOS1 protein function. 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.
Ambry Genetics RCV002421259 SCV002718423 likely benign Cardiovascular phenotype 2024-09-21 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genome-Nilou Lab RCV002468303 SCV002763348 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002468302 SCV002763349 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing

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