Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000038531 | SCV000062209 | pathogenic | Noonan syndrome | 2013-02-19 | criteria provided, single submitter | clinical testing | The Lys728Ile variant in SOS1 has been reported in the literature in one patient with clinical features of Noonan Syndrome and the presence of embryonal rhabdom yosarcoma (Jongmans 2010). The variant was reported to have occurred de novo in this patient and this finding supports a pathogenic role. In addition, this var iant was identified to have occurred de novo in one proband with clinical featur es of Noonan syndrome by our laboratory. Computational analyses (biochemical ami no acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that t he Lys728Ile variant may impact the protein. In addition, this variant has not b een identified in large and broad populations by the NHLBI Exome Sequencing Proj ect (Lepri 2011, http://evs.gs.washington.edu/EVS/). In summary, this variant me ets our criteria to be classified as pathogenic (http://pcpgm.partners.org/LMM) |
Gene |
RCV000159126 | SCV000209070 | likely pathogenic | not provided | 2023-08-04 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 20461756, 21387466, 29493581, 23885229, 35386434, 34204435, 26173643) |
Molecular Diagnostics Lab, |
RCV000495874 | SCV000583559 | likely pathogenic | Noonan syndrome 4 | 2017-06-21 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001045366 | SCV001209211 | pathogenic | RASopathy | 2021-01-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with clinical features of RASopathy disorders (PMID: 20461756, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 40699). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with isoleucine at codon 728 of the SOS1 protein (p.Lys728Ile). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and isoleucine. |
Genome- |
RCV000495874 | SCV002763324 | likely pathogenic | Noonan syndrome 4 | criteria provided, single submitter | clinical testing |