Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000705710 | SCV000834721 | uncertain significance | Peutz-Jeghers syndrome | 2018-05-07 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glutamic acid at codon 176 of the STK11 protein (p.Asp176Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with STK11-related 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. The p.Asp176 amino acid residue in STK11 has been determined to be clinically significant (PMID: 9399902, 24652667, 24604241, 17924967, 837816, 10441497, 15987703). This suggests that variants that disrupt this residue are likely to be causative of disease. 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. |