ClinVar Miner

Submissions for variant NM_020975.6(RET):c.3052C>T (p.Leu1018Phe)

gnomAD frequency: 0.00001  dbSNP: rs766330880
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000654577 SCV000776471 uncertain significance Multiple endocrine neoplasia, type 2 2023-12-28 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1018 of the RET protein (p.Leu1018Phe). This variant is present in population databases (rs766330880, gnomAD 0.01%). This missense change has been observed in individual(s) with medullary thyroid carcinoma (PMID: 33827484). ClinVar contains an entry for this variant (Variation ID: 543741). 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.
Mendelics RCV000709125 SCV000838408 uncertain significance Multiple endocrine neoplasia, type 2a 2018-07-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV001018329 SCV001179553 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-01 criteria provided, single submitter clinical testing The p.L1018F variant (also known as c.3052C>T), located in coding exon 19 of the RET gene, results from a C to T substitution at nucleotide position 3052. The leucine at codon 1018 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration was identified in 1/245 Chinese patients with medullary thyroid carcinoma (Qi XP et al. BMC Cancer, 2021 Apr;21:369). This amino acid position is highly 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.
Illumina Laboratory Services, Illumina RCV001106020 SCV001263044 uncertain significance Pheochromocytoma 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001106021 SCV001263045 uncertain significance Renal hypodysplasia/aplasia 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001106022 SCV001263046 uncertain significance Hirschsprung disease, susceptibility to, 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001106023 SCV001263047 likely benign Multiple endocrine neoplasia 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx RCV003318621 SCV004022723 uncertain significance not provided 2023-07-21 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 14633923, 33827484)
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003493698 SCV004243366 uncertain significance not specified 2024-02-06 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.