Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001046163 | SCV001210053 | uncertain significance | Tuberous sclerosis 2 | 2021-09-25 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with tyrosine at codon 891 of the TSC2 protein (p.His891Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. 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. 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 not been reported in the literature in individuals affected with TSC2-related conditions. |
| Ambry Genetics | RCV002429615 | SCV002741301 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-20 | criteria provided, single submitter | clinical testing | The p.H891Y variant (also known as c.2671C>T), located in coding exon 23 of the TSC2 gene, results from a C to T substitution at nucleotide position 2671. The histidine at codon 891 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |