Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001267314 | SCV001445495 | likely pathogenic | Inborn genetic diseases | 2021-02-24 | criteria provided, single submitter | clinical testing | The c.1648C>G (p.R550G) alteration is located in coding exon 10 of the SOS2 gene. This alteration results from a C to G substitution at nucleotide position 1648, causing the arginine (R) at amino acid position 550 to be replaced by a glycine (G). Based on data from the Genome Aggregation Database (gnomAD), the SOS2 c.1648C>G alteration was not observed, with coverage at this position. Multiple disease-causing alterations at the amino acid position corresponding to SOS2 p.R550 in a paralogous protein, SOS1, have been reported in affected individuals; these include SOS1 p.R552G, p.R552S, and p.R552K which have been reported in individuals with Noonan-syndrome and related disorders, including familial and de novo occurrences (Tartaglia, 2007; Roberts, 2007; Zenker, 2007; Neumann, 2009; Denayer, 2010; Ceyhan-Birsoy, 2018; Beneteau, 2009; Calcagni, 2016). This amino acid position is highly conserved in available vertebrate species. The p.R550G alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. |
MGZ Medical Genetics Center | RCV002290676 | SCV002579560 | uncertain significance | Noonan syndrome 9 | 2021-11-04 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003908485 | SCV004725542 | uncertain significance | SOS2-related condition | 2023-10-27 | criteria provided, single submitter | clinical testing | The SOS2 c.1648C>G variant is predicted to result in the amino acid substitution p.Arg550Gly. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |