Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000530391 | SCV000658451 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-09-30 | 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 477350). This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 808 of the RET protein (p.Lys808Glu). |
| Ambry Genetics | RCV001015469 | SCV001176305 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-21 | criteria provided, single submitter | clinical testing | The p.K808E variant (also known as c.2422A>G), located in coding exon 14 of the RET gene, results from an A to G substitution at nucleotide position 2422. The lysine at codon 808 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV000530391 | SCV004357249 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-05-11 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamic acid at codon 808 of the RET protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with medullary thyroid cancer (DOI: 10.1007/s00423-013-1109-y). 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. |
| All of Us Research Program, |
RCV000530391 | SCV004838670 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-02-24 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamic acid at codon 808 of the RET protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with medullary thyroid cancer (DOI: 10.1007/s00423-013-1109-y). 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. |