ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.2489A>T (p.Asn830Ile)

dbSNP: rs397517158
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000038534 SCV000062212 uncertain significance not specified 2021-01-28 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV001753449 SCV001986649 uncertain significance not provided 2018-09-30 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 a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001852806 SCV002272226 uncertain significance RASopathy 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 830 of the SOS1 protein (p.Asn830Ile). 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: 45352). 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. 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.
Genome-Nilou Lab RCV002467544 SCV002763301 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002467543 SCV002763302 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing
Ambry Genetics RCV004018876 SCV004957693 uncertain significance Cardiovascular phenotype 2024-05-11 criteria provided, single submitter clinical testing The p.N830I variant (also known as c.2489A>T), located in coding exon 15 of the SOS1 gene, results from an A to T substitution at nucleotide position 2489. The asparagine at codon 830 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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