Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001046337 | SCV001210234 | uncertain significance | Peutz-Jeghers syndrome | 2019-07-06 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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 disrupts the p.Trp308 amino acid residue in STK11. Other variant(s) that disrupt this residue have been observed in individuals with STK11-related conditions (PMID: 9837816, 23415580, 24604241), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with STK11-related conditions. This sequence change replaces tryptophan with arginine at codon 308 of the STK11 protein (p.Trp308Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. |