ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2116G>A (p.Val706Met)

gnomAD frequency: 0.00006  dbSNP: rs137855422
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409130 SCV000489775 uncertain significance Multiple endocrine neoplasia type 2B 2015-12-28 criteria provided, single submitter clinical testing
Counsyl RCV000410654 SCV000489776 uncertain significance Multiple endocrine neoplasia type 2A 2015-12-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000565078 SCV000674858 benign Hereditary cancer-predisposing syndrome 2023-03-12 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Mendelics RCV000410654 SCV000838395 uncertain significance Multiple endocrine neoplasia type 2A 2018-07-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000795272 SCV000934721 uncertain significance Multiple endocrine neoplasia, type 2 2023-12-27 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 706 of the RET protein (p.Val706Met). This variant is present in population databases (rs137855422, gnomAD 0.02%). This missense change has been observed in individual(s) with endometrial cancer and/or breast cancer (PMID: 29625052, 35264596, 36451132). ClinVar contains an entry for this variant (Variation ID: 372079). 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.
Myriad Genetics, Inc. RCV000410654 SCV004018052 likely benign Multiple endocrine neoplasia type 2A 2024-08-12 criteria provided, single submitter clinical testing This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.
All of Us Research Program, National Institutes of Health RCV000795272 SCV004838656 uncertain significance Multiple endocrine neoplasia, type 2 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces valine with methionine at codon 706 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 been reported in an individual affected with cervical adenocarcinoma (PMID: 27683183). This variant has been identified in 5/247968 chromosomes 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.
Baylor Genetics RCV004567897 SCV005054203 uncertain significance Hirschsprung disease, susceptibility to, 1 2024-01-21 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.