ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.2158A>G (p.Thr720Ala)

gnomAD frequency: 0.00001  dbSNP: rs367634525
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Johns Hopkins Genomics, Johns Hopkins University RCV001290370 SCV001478423 uncertain significance Noonan syndrome 4 2021-01-21 criteria provided, single submitter clinical testing This SOS1 variant (rs367634525) is rare (<0.1%) in a large population dataset (gnomAD: 3/250686 total alleles; 0.0012%; no homozygotes) and has not been reported in ClinVar nor the literature, to our knowledge. Three bioinformatic tools queried predict that the substitution would be tolerated, but these algorithms have low specificity, especially for predicting gain of function variants. The threonine residue at this position is evolutionarily conserved in most species assessed, except fish. We consider the clinical significance of c.2158A>G to be uncertain at this time.
GeneDx RCV001587319 SCV001815516 uncertain significance not provided 2019-07-23 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Missense variants in this gene are commonly 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
Ambry Genetics RCV002418880 SCV002724632 likely benign Cardiovascular phenotype 2023-11-17 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 RCV001290370 SCV002763329 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002468214 SCV002763331 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002504421 SCV002816232 uncertain significance Fibromatosis, gingival, 1; Noonan syndrome 4 2021-09-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002538392 SCV003284897 benign RASopathy 2024-11-11 criteria provided, single submitter clinical testing

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