Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001264556 | SCV001442765 | uncertain significance | not specified | 2020-10-01 | criteria provided, single submitter | clinical testing | Variant summary: SOS2 c.3788C>G (p.Pro1263Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251450 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.3788C>G in individuals affected with Noonan Syndrome 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. |
Labcorp Genetics |
RCV001365570 | SCV001561845 | likely benign | Noonan syndrome 9 | 2024-01-08 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001365570 | SCV002762972 | uncertain significance | Noonan syndrome 9 | criteria provided, single submitter | clinical testing | ||
Ambry Genetics | RCV004035418 | SCV003591052 | uncertain significance | Cardiovascular phenotype | 2023-01-19 | criteria provided, single submitter | clinical testing | The p.P1263R variant (also known as c.3788C>G), located in coding exon 23 of the SOS2 gene, results from a C to G substitution at nucleotide position 3788. The proline at codon 1263 is replaced by arginine, an amino acid with dissimilar 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. |
Prevention |
RCV004746300 | SCV005346733 | uncertain significance | SOS2-related disorder | 2024-03-15 | no assertion criteria provided | clinical testing | The SOS2 c.3788C>G variant is predicted to result in the amino acid substitution p.Pro1263Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0065% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |