Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000190032 | SCV000243705 | uncertain significance | not provided | 2014-04-02 | criteria provided, single submitter | clinical testing | p.Ser1452Leu (TCG>TTG): c.4355 C>T in exon 34 of the TSC2 gene (NM_000548.3) The S1452L variant was previously reported as S1453L and was considered a benign polymorphism, although no additional information was provided (Au et al., 2007). According to the TSC2 LOVD Variant Database, it was identified in a patient with clinical features of tuberous sclerosis but was also identified in an unaffected parent. 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. The S1452L 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. However, this substitution does not occur within known functional domains of the tuberin protein, where many pathogenic missense mutations have been identified (Northrup et al., 2011; Au et al., 2007). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The variant is found in EPILEPSY panel(s). |
| Invitae | RCV001088217 | SCV000544375 | likely benign | Tuberous sclerosis 2 | 2023-12-06 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001022345 | SCV001184070 | likely benign | Hereditary cancer-predisposing syndrome | 2022-07-29 | 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- |
RCV001088217 | SCV002039856 | uncertain significance | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Tuberous sclerosis database |
RCV000043095 | SCV000066894 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |