Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001224702 | SCV001396917 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 20 of the RET protein (p.Pro20Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 952569). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 | RCV002356955 | SCV002657153 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-13 | criteria provided, single submitter | clinical testing | The p.P20Q variant (also known as c.59C>A), located in coding exon 1 of the RET gene, results from a C to A substitution at nucleotide position 59. The proline at codon 20 is replaced by glutamine, an amino acid with similar properties. This amino acid position is conserved. 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. |
| Fulgent Genetics, |
RCV002504291 | SCV002816407 | uncertain significance | Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A | 2021-09-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003442787 | SCV004170719 | uncertain significance | not provided | 2023-11-06 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| All of Us Research Program, |
RCV001224702 | SCV004830554 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-09-17 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with glutamine at codon 20 of the RET protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RET-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |