ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.257C>T (p.Ala86Val)

gnomAD frequency: 0.00004  dbSNP: rs146272145
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000801445 SCV000941221 uncertain significance Noonan syndrome 9 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 86 of the SOS2 protein (p.Ala86Val). This variant is present in population databases (rs146272145, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with SOS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 647039). 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 SOS2 protein function with a positive predictive value of 95%. 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 RCV002458466 SCV002739600 uncertain significance Cardiovascular phenotype 2021-07-27 criteria provided, single submitter clinical testing The p.A86V variant (also known as c.257C>T), located in coding exon 3 of the SOS2 gene, results from a C to T substitution at nucleotide position 257. The alanine at codon 86 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000801445 SCV002763147 uncertain significance Noonan syndrome 9 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000801445 SCV002785817 uncertain significance Noonan syndrome 9 2021-09-07 criteria provided, single submitter clinical testing

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