Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000196130 | SCV000255047 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-12-20 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 633 of the RET protein (p.Leu633Val). This variant is present in population databases (rs267607010, gnomAD 0.01%). This missense change has been observed in individual(s) with breast cancer (PMID: 36315513). This missense change has been observed to co-occur in individuals with a different variant in RET that has been determined to be pathogenic (PMID: 8099202), but the significance of this finding is unclear. ClinVar contains an entry for this variant (Variation ID: 216718). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV000410079 | SCV000489999 | uncertain significance | Multiple endocrine neoplasia, type 2b | 2016-09-13 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000411153 | SCV000490000 | uncertain significance | Multiple endocrine neoplasia, type 2a | 2016-09-13 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV002478712 | SCV002774861 | uncertain significance | not provided | 2021-08-18 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002503784 | SCV002816466 | uncertain significance | Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia, type 2b; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia, type 2a | 2022-04-14 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003165476 | SCV003911390 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-18 | criteria provided, single submitter | clinical testing | The p.L633V variant (also known as c.1897C>G), located in coding exon 11 of the RET gene, results from a C to G substitution at nucleotide position 1897. The leucine at codon 633 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Myriad Genetics, |
RCV000411153 | SCV004018502 | 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. |