Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000371601 | SCV000330447 | uncertain significance | not provided | 2016-04-25 | criteria provided, single submitter | clinical testing | The L1233I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although the L1233I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, this substitution does occur at a position that is conserved across species. Finally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
Labcorp Genetics |
RCV001859536 | SCV002194312 | uncertain significance | RASopathy | 2021-02-14 | criteria provided, single submitter | clinical testing | 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with SOS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 280523). This variant is present in population databases (rs777373438, ExAC 0.009%). This sequence change replaces leucine with isoleucine at codon 1233 of the SOS1 protein (p.Leu1233Ile). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and isoleucine. |
Genome- |
RCV002467706 | SCV002763553 | uncertain significance | Noonan syndrome 4 | criteria provided, single submitter | clinical testing | ||
Genome- |
RCV002467705 | SCV002763554 | uncertain significance | Fibromatosis, gingival, 1 | criteria provided, single submitter | clinical testing | ||
Service de Génétique Moléculaire, |
RCV001261114 | SCV001438521 | likely benign | Noonan syndrome | no assertion criteria provided | clinical testing |