Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000474131 | SCV000552308 | uncertain significance | Tuberous sclerosis 1 | 2018-03-21 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 300 of the TSC1 protein (p.Thr300Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs370916731, ExAC 0.003%). This variant has not been reported in the literature in individuals with TSC1-related disease. ClinVar contains an entry for this variant (Variation ID: 411242). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
| Ambry Genetics | RCV000561523 | SCV000675410 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-07-03 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient evidence |