Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Johns Hopkins Genomics, |
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. |
Gene |
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 | uncertain significance | Cardiovascular phenotype | 2021-05-08 | criteria provided, single submitter | clinical testing | The p.T720A variant (also known as c.2158A>G), located in coding exon 13 of the SOS1 gene, results from an A to G substitution at nucleotide position 2158. The threonine at codon 720 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Genome- |
RCV001290370 | SCV002763329 | uncertain significance | Noonan syndrome 4 | criteria provided, single submitter | clinical testing | ||
Genome- |
RCV002468214 | SCV002763331 | uncertain significance | Fibromatosis, gingival, 1 | criteria provided, single submitter | clinical testing | ||
Fulgent Genetics, |
RCV002504421 | SCV002816232 | uncertain significance | Fibromatosis, gingival, 1; Noonan syndrome 4 | 2021-09-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002538392 | SCV003284897 | benign | RASopathy | 2023-12-20 | criteria provided, single submitter | clinical testing |