ClinVar Miner

Submissions for variant NM_020975.6(RET):c.335G>A (p.Arg112His)

gnomAD frequency: 0.00002  dbSNP: rs587780814
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000123322 SCV000166629 uncertain significance Multiple endocrine neoplasia, type 2 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 112 of the RET protein (p.Arg112His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 136120). 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.
Counsyl RCV000411433 SCV000489751 uncertain significance Multiple endocrine neoplasia type 2B 2015-12-04 criteria provided, single submitter clinical testing
Counsyl RCV000409019 SCV000489752 uncertain significance Multiple endocrine neoplasia type 2A 2015-12-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000563716 SCV000674872 likely benign Hereditary cancer-predisposing syndrome 2023-05-26 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
CeGaT Center for Human Genetics Tuebingen RCV001310569 SCV001500425 uncertain significance not provided 2020-08-01 criteria provided, single submitter clinical testing
GeneDx RCV001310569 SCV003918286 uncertain significance not provided 2022-10-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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.