ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1018G>T (p.Val340Phe)

gnomAD frequency: 0.00003  dbSNP: rs367737920
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
Invitae RCV000470605 SCV000543821 uncertain significance Multiple endocrine neoplasia, type 2 2023-11-10 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 340 of the RET protein (p.Val340Phe). This variant is present in population databases (rs367737920, gnomAD 0.007%). 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: 405542). 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 tolerated. 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 RCV000662822 SCV000785665 uncertain significance Multiple endocrine neoplasia, type 2a 2017-10-24 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV002256246 SCV002529906 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-10 criteria provided, single submitter curation
Ambry Genetics RCV002256246 SCV002657646 uncertain significance Hereditary cancer-predisposing syndrome 2021-03-24 criteria provided, single submitter clinical testing The p.V340F variant (also known as c.1018G>T), located in coding exon 5 of the RET gene, results from a G to T substitution at nucleotide position 1018. The valine at codon 340 is replaced by phenylalanine, 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, Inc. RCV000662822 SCV004018051 uncertain significance Multiple endocrine neoplasia, type 2a 2023-04-17 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.
GeneDx RCV003327399 SCV004034611 uncertain significance not provided 2023-03-06 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; This variant is associated with the following publications: (PMID: 14633923)

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.