Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174628 | SCV001337834 | uncertain significance | not specified | 2020-01-20 | criteria provided, single submitter | clinical testing | Variant summary: SOS2 c.189G>C (p.Gln63His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 246190 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.189G>C in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002411671 | SCV002723609 | uncertain significance | Cardiovascular phenotype | 2021-10-12 | criteria provided, single submitter | clinical testing | The p.Q63H variant (also known as c.189G>C), located in coding exon 2 of the SOS2 gene, results from a G to C substitution at nucleotide position 189. The glutamine at codon 63 is replaced by histidine, an amino acid with highly 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- |
RCV002468181 | SCV002763151 | uncertain significance | Noonan syndrome 9 | criteria provided, single submitter | clinical testing |