Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001539167 | SCV001756911 | uncertain significance | not provided | 2021-01-14 | criteria provided, single submitter | clinical testing | Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002386442 | SCV002689865 | uncertain significance | Cardiovascular phenotype | 2022-08-24 | criteria provided, single submitter | clinical testing | The p.K435E variant (also known as c.1303A>G), located in coding exon 10 of the SOS1 gene, results from an A to G substitution at nucleotide position 1303. The lysine at codon 435 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Genome- |
RCV002468264 | SCV002763431 | uncertain significance | Noonan syndrome 4 | criteria provided, single submitter | clinical testing | ||
Genome- |
RCV002468263 | SCV002763432 | uncertain significance | Fibromatosis, gingival, 1 | criteria provided, single submitter | clinical testing | ||
Fulgent Genetics, |
RCV002501873 | SCV002805587 | uncertain significance | Fibromatosis, gingival, 1; Noonan syndrome 4 | 2021-10-05 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002570639 | SCV003444031 | uncertain significance | RASopathy | 2022-05-25 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 435 of the SOS1 protein (p.Lys435Glu). 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: 1181716). 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 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. |