Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001211988 | SCV001383557 | uncertain significance | Peutz-Jeghers syndrome | 2019-09-10 | criteria provided, single submitter | clinical testing | 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. 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 has not been reported in the literature in individuals with STK11-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with tyrosine at codon 154 of the STK11 protein (p.His154Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. |
| Ambry Genetics | RCV002339549 | SCV002637753 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-28 | criteria provided, single submitter | clinical testing | The p.H154Y variant (also known as c.460C>T), located in coding exon 3 of the STK11 gene, results from a C to T substitution at nucleotide position 460. The histidine at codon 154 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |