Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001015120 | SCV001175917 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-26 | criteria provided, single submitter | clinical testing | The p.P767H variant (also known as c.2300C>A), located in coding exon 14 of the DICER1 gene, results from a C to A substitution at nucleotide position 2300. The proline at codon 767 is replaced by histidine, an amino acid with similar properties. This amino acid position is well 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. |
| Invitae | RCV001065902 | SCV001230892 | uncertain significance | DICER1-related tumor predisposition | 2019-11-21 | criteria provided, single submitter | clinical testing | 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with DICER1-related conditions. This variant is present in population databases (rs764001016, ExAC 0.009%). This sequence change replaces proline with histidine at codon 767 of the DICER1 protein (p.Pro767His). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and histidine. |