Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001349277 | SCV001543612 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2022-11-08 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 189 of the RET protein (p.Arg189Cys). This variant has not been reported in the literature in individuals affected with RET-related conditions. 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1044947). |
Ambry Genetics | RCV002350650 | SCV002651871 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-07 | criteria provided, single submitter | clinical testing | The p.R189C variant (also known as c.565C>T), located in coding exon 3 of the RET gene, results from a C to T substitution at nucleotide position 565. The arginine at codon 189 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not 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. |
Fulgent Genetics, |
RCV002493796 | SCV002799762 | uncertain significance | Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A | 2022-04-22 | criteria provided, single submitter | clinical testing |