Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genome Diagnostics Laboratory, |
RCV001813626 | SCV002060663 | benign | Noonan syndrome and Noonan-related syndrome | 2020-04-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002074230 | SCV002388844 | likely benign | Noonan syndrome 9 | 2023-03-07 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271674 | SCV002555933 | likely benign | not specified | 2022-06-16 | criteria provided, single submitter | clinical testing | Variant summary: SOS2 c.1211C>T (p.Pro404Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.8e-05 in 248048 control chromosomes, predominantly at a frequency of 0.00066 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 264 fold of the estimated maximal expected allele frequency for a pathogenic variant in SOS2 causing Noonan Syndrome phenotype (2.5e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.1211C>T in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as benign and likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |
| Genome- |
RCV002074230 | SCV002763091 | likely benign | Noonan syndrome 9 | criteria provided, single submitter | clinical testing |