Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000497607 | SCV000590233 | uncertain significance | not provided | 2017-06-06 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the TSC2 gene. The S1507F variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S1507F variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The S1507F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Multiple missense variants in nearby residues have been reported in Human Gene Mutation Database in association with tuberous sclerosis (Stenson et al., 2014), supporting the functional importance of this region of the protein. However, this substitution does not occur within known functional domains of the tuberin protein, where many pathogenic missense variants have been identified (Northrup et al., 2011; Au et al., 2007). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV001078813 | SCV000765938 | likely benign | Tuberous sclerosis 2 | 2024-01-12 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001022632 | SCV001184391 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Genome- |
RCV001078813 | SCV002040201 | likely benign | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing |