Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000456854 | SCV000543825 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 844 of the RET protein (p.Arg844Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Hirschsprung’s disease (PMID: 16818057). ClinVar contains an entry for this variant (Variation ID: 24950). An algorithm developed specifically for the RET gene suggests that this missense change is likely to be deleterious (PMID: 21479187). 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. |
Counsyl | RCV000662786 | SCV000785595 | uncertain significance | Multiple endocrine neoplasia type 2A | 2017-09-29 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001015858 | SCV001176738 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-16 | criteria provided, single submitter | clinical testing | The p.R844W variant (also known as c.2530C>T), located in coding exon 14 of the RET gene, results from a C to T substitution at nucleotide position 2530. The arginine at codon 844 is replaced by tryptophan, an amino acid with dissimilar 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. |
Gene |
RCV001588822 | SCV001815392 | uncertain significance | not provided | 2019-09-06 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Observed in a patient with Hirschprung disease (Kim 2006); This variant is associated with the following publications: (PMID: 16818057, 21479187) |
Fulgent Genetics, |
RCV002482896 | SCV002785379 | uncertain significance | Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A | 2022-05-09 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000662786 | SCV004018477 | uncertain significance | Multiple endocrine neoplasia type 2A | 2023-04-18 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
Baylor Genetics | RCV003460491 | SCV004208681 | uncertain significance | Hirschsprung disease, susceptibility to, 1 | 2024-02-08 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000456854 | SCV005430386 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-09-09 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with tryptophan at codon 844 of the RET protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. Two other missense variants at this position, p.Arg844Leu and p.Arg844Gln, have been reported individuals affected with medullary thyroid cancer or pheochromocytoma (PMID: 9506724, 10826520, 18058472, 30877234). 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. |