ClinVar Genomic variation as it relates to human health
NM_020975.4(RET):c.[2410G>A;2832C>G]
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
NM_020975.4(RET):c.[2410G>A;2832C>G]
- Other names
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- Functional consequence
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- Links
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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RET | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3446 | 3566 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
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The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, single submitter
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Jun 15, 2016 | RCV000757883.12 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
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Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jun 15, 2016)
|
criteria provided, single submitter
Method: clinical testing
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Medullary thyroid carcinoma
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Columbia University Laboratory of Personalized Genomic Medicine, Columbia University Medical Center
Accession: SCV000882830.1
First in ClinVar: Feb 18, 2019 Last updated: Feb 18, 2019 |
Sex: male
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Multiple Endocrine Neoplasia Type 2. | Adam MP | - | 2023 | PMID: 20301434 |
Controversy on the management of patients carrying RET p.V804M mutation. | Alzahrani AS | Endocrine | 2022 | PMID: 34637071 |
Case report of adrenocortical carcinoma associated with double germline mutations in MSH2 and RET. | Raygada M | American journal of medical genetics. Part A | 2021 | PMID: 33615670 |
Homozygosity for the pathogenic RET hotspot variant p.Cys634Trp: A consanguineous family with MEN2A. | Schirwani S | European journal of medical genetics | 2021 | PMID: 33450337 |
Results and Clinical Interpretation of Germline RET Analysis in a Series of Patients with Medullary Thyroid Carcinoma: The Challenge of the Variants of Uncertain Significance. | Innella G | Cancers | 2020 | PMID: 33167350 |
Emergence and Targeting of Acquired and Hereditary Resistance to Multikinase RET Inhibition in Patients With RET-Altered Cancer. | Wirth LJ | JCO precision oncology | 2019 | PMID: 32923848 |
Twenty-Five Years Experience on RET Genetic Screening on Hereditary MTC: An Update on The Prevalence of Germline RET Mutations. | Elisei R | Genes | 2019 | PMID: 31510104 |
Identification of a secondary RET mutation in a pediatric patient with relapsed acute myeloid leukemia leads to the diagnosis and treatment of asymptomatic metastatic medullary thyroid cancer in a parent: a case for sequencing the germline. | Pendrick DM | Cold Spring Harbor molecular case studies | 2019 | PMID: 30936199 |
p.Val804Met, the Most Frequent Pathogenic Mutation in RET, Confers a Very Low Lifetime Risk of Medullary Thyroid Cancer. | Loveday C | The Journal of clinical endocrinology and metabolism | 2018 | PMID: 29590403 |
Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study. | Ghazani AA | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 28125075 |
How to Assess the Clinical Relevance of Novel RET Missense Variants in the Absence of Functional Studies? | Karrasch T | European thyroid journal | 2016 | PMID: 27099842 |
Distribution of RET Mutations and Evaluation of Treatment Approaches in Hereditary Medullary Thyroid Carcinoma in Turkey. | Aydoğan Bİ | Journal of clinical research in pediatric endocrinology | 2016 | PMID: 26758973 |
Identification of Novel Small Molecule Inhibitors of Oncogenic RET Kinase. | Moccia M | PloS one | 2015 | PMID: 26046350 |
C-Cell Neoplasia in Asymptomatic Carriers of RET Mutation in Extracellular Cysteine-Rich and Intracellular Tyrosine Kinase Domain. | Abi-Raad R | Human pathology | 2015 | PMID: 26033033 |
Papillary thyroid carcinoma and multiple endocrine neoplasia type 2. | Febrero B | Journal of endocrinological investigation | 2015 | PMID: 25903693 |
Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. | Wells SA Jr | Thyroid : official journal of the American Thyroid Association | 2015 | PMID: 25810047 |
Genetic screening of patients with medullary thyroid cancer in a referral center in Greece during the past two decades. | Sarika HL | European journal of endocrinology | 2015 | PMID: 25624014 |
Characterization of V804M-mutated RET proto-oncogene associated with familial medullary thyroid cancer, report of the largest Turkish family. | Basaran MN | Journal of endocrinological investigation | 2015 | PMID: 25501606 |
Twenty years of lesson learning: how does the RET genetic screening test impact the clinical management of medullary thyroid cancer? | Romei C | Clinical endocrinology | 2015 | PMID: 25440022 |
Tandem Germline RET Mutations in a Family Pathogenetic for Multiple Endocrine Neoplasia 2B, Confirmed by a Natural Experiment. | Kihara M | European thyroid journal | 2014 | PMID: 25759805 |
Alectinib shows potent antitumor activity against RET-rearranged non-small cell lung cancer. | Kodama T | Molecular cancer therapeutics | 2014 | PMID: 25349307 |
Prevalence by age and predictors of medullary thyroid cancer in patients with lower risk germline RET proto-oncogene mutations. | Rich TA | Thyroid : official journal of the American Thyroid Association | 2014 | PMID: 24617864 |
Oncogenic RET kinase domain mutations perturb the autophosphorylation trajectory by enhancing substrate presentation in trans. | Plaza-Menacho I | Molecular cell | 2014 | PMID: 24560924 |
Patient affected by neurofibromatosis type 1 and thyroid C-cell hyperplasia harboring pathogenic germ-line mutations in both NF1 and RET genes. | Ercolino T | Gene | 2014 | PMID: 24361808 |
In silico profiling and structural insights of missense mutations in RET protein kinase domain by molecular dynamics and docking approach. | George Priya Doss C | Molecular bioSystems | 2014 | PMID: 24336963 |
The optimal range of RET mutations to be tested: European comments to the guidelines of the American Thyroid Association. | Fugazzola L | Thyroid research | 2013 | PMID: 23514012 |
Novel tandem germline RET proto-oncogene mutations in a patient with multiple endocrine neoplasia type 2B: report of a case and a literature review of tandem RET mutations with in silico analysis. | Nakao KT | Head & neck | 2013 | PMID: 23468374 |
A Case of medullary thyroid carcinoma with de novo V804M RET germline mutation. | Choi YS | Journal of Korean medical science | 2013 | PMID: 23341727 |
In silico and in vitro analysis of rare germline allelic variants of RET oncogene associated with medullary thyroid cancer. | Cosci B | Endocrine-related cancer | 2011 | PMID: 21810974 |
Focal adhesion kinase (FAK) binds RET kinase via its FERM domain, priming a direct and reciprocal RET-FAK transactivation mechanism. | Plaza-Menacho I | The Journal of biological chemistry | 2011 | PMID: 21454698 |
Molecular analysis of the RET proto-oncogene key exons in patients with medullary thyroid carcinoma: a comprehensive study of the Iranian population. | Alvandi E | Thyroid : official journal of the American Thyroid Association | 2011 | PMID: 21309721 |
RET codon 804 mutations in multiple endocrine neoplasia 2: genotype-phenotype correlations and implications in clinical management. | Mukherjee S | Clinical genetics | 2011 | PMID: 20497437 |
Single nucleotide polymorphisms act as modifiers and correlate with the development of medullary and simultaneous medullary/papillary thyroid carcinomas in 2 large, non-related families with the RET V804M proto-oncogene mutation. | Shifrin AL | Surgery | 2010 | PMID: 21134561 |
One hundred and seven member family with the rearranged during transfection V804M proto-oncogene mutation presenting with simultaneous medullary and papillary thyroid carcinomas, rare primary hyperparathyroidism, and no pheochromocytomas: Is this a new syndrome-MEN 2C? | Shifrin AL | Surgery | 2010 | PMID: 20719260 |
Multiple endocrine neoplasia type 2 syndromes (MEN 2): results from the ItaMEN network analysis on the prevalence of different genotypes and phenotypes. | Romei C | European journal of endocrinology | 2010 | PMID: 20516206 |
Simultaneous medullary and papillary thyroid carcinomas in carriers of the V804M RET germline mutation-a spurious association? | Machens A | Surgery | 2010 | PMID: 20494215 |
Synchronous metastatic medullary and papillary thyroid carcinomas in a patient with germline RET mutation: case report, molecular analysis, and implications for pathogenesis. | Griffith C | Endocrine pathology | 2010 | PMID: 20369307 |
Kindred with prominent corneal nerves associated with a mutation in codon 804 of RET on chromosome 10q11. | Ong DS | Archives of ophthalmology (Chicago, Ill. : 1960) | 2010 | PMID: 20142552 |
A novel de novo germ-line V292M mutation in the extracellular region of RET in a patient with phaeochromocytoma and medullary thyroid carcinoma: functional characterization. | Castellone MD | Clinical endocrinology | 2010 | PMID: 20039896 |
Familial medullary thyroid carcinoma associated with cutaneous lichen amyloidosis. | Rothberg AE | Thyroid : official journal of the American Thyroid Association | 2009 | PMID: 19445625 |
Uncommon association of germline mutations of RET proto-oncogene and CDKN2A gene. | Foppiani L | European journal of endocrinology | 2008 | PMID: 18299477 |
Familial prevalence and age of RET germline mutations: implications for screening. | Machens A | Clinical endocrinology | 2008 | PMID: 18062802 |
RET genetic screening in patients with medullary thyroid cancer and their relatives: experience with 807 individuals at one center. | Elisei R | The Journal of clinical endocrinology and metabolism | 2007 | PMID: 17895320 |
Sorafenib functions to potently suppress RET tyrosine kinase activity by direct enzymatic inhibition and promoting RET lysosomal degradation independent of proteasomal targeting. | Plaza-Menacho I | The Journal of biological chemistry | 2007 | PMID: 17664273 |
Asymptomatic bilateral adrenal pheochromocytoma in a patient with a germline V804M mutation in the RET proto-oncogene. | Recasens M | Clinical endocrinology | 2007 | PMID: 17466010 |
RET proto-oncogene in Sardinia: V804M is the most frequent mutation and may be associated with FMTC/MEN-2A phenotype. | Pinna G | Thyroid : official journal of the American Thyroid Association | 2007 | PMID: 17316110 |
RET is constitutively activated by novel tandem mutations that alter the active site resulting in multiple endocrine neoplasia type 2B. | Cranston AN | Cancer research | 2006 | PMID: 17047083 |
Inhibition of RET tyrosine kinase by SU5416. | Mologni L | Journal of molecular endocrinology | 2006 | PMID: 17032739 |
Long-term outcome in 46 gene carriers of hereditary medullary thyroid carcinoma after prophylactic thyroidectomy: impact of individual RET genotype. | Frank-Raue K | European journal of endocrinology | 2006 | PMID: 16868135 |
Genotype-phenotype correlations in Hungarian patients with hereditary medullary thyroid cancer. | Patocs A | Wiener klinische Wochenschrift | 2006 | PMID: 16865647 |
Experience of prophylactic thyroidectomy in multiple endocrine neoplasia type 2A kindreds with RET codon 804 mutations. | Learoyd DL | Clinical endocrinology | 2005 | PMID: 16343097 |
Germline homozygous mutations at codon 804 in the RET protooncogene in medullary thyroid carcinoma/multiple endocrine neoplasia type 2A patients. | Lesueur F | The Journal of clinical endocrinology and metabolism | 2005 | PMID: 15741265 |
Germline RET V804M mutation associated with multiple endocrine neoplasia type 2A. | Gibelin H | The British journal of surgery | 2004 | PMID: 15386323 |
Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitors. | Carlomagno F | Oncogene | 2004 | PMID: 15184865 |
Primary hyperparathyroidism, C-cell hyperplasia and papillary thyroid carcinoma in a patient with RET germline polymorphism S836S. | Brauckhoff M | Langenbeck's archives of surgery | 2002 | PMID: 12410354 |
Papillary thyroid carcinoma in patients with RET proto-oncogene germline mutation. | Brauckhoff M | Thyroid : official journal of the American Thyroid Association | 2002 | PMID: 12193298 |
V804M RET mutation and familial medullary thyroid carcinoma: report of a large family with expression of the disease only in the homozygous gene carriers. | Lecube A | Surgery | 2002 | PMID: 12019403 |
Atypical MEN type 2B associated with two germline RET mutations on the same allele not involving codon 918. | Menko FH | The Journal of clinical endocrinology and metabolism | 2002 | PMID: 11788682 |
Familial medullary thyroid carcinoma and prominent corneal nerves associated with the germline V804M and V778I mutations on the same allele of RET. | Kasprzak L | Journal of medical genetics | 2001 | PMID: 11732489 |
Genotype-phenotype correlations in hereditary medullary thyroid carcinoma: oncological features and biochemical properties. | Machens A | The Journal of clinical endocrinology and metabolism | 2001 | PMID: 11238493 |
Update on the MEN 2A c804 RET mutation: is prophylactic thyroidectomy indicated? | Frohnauer MK | Surgery | 2000 | PMID: 11114642 |
Variable expressivity of familial medullary thyroid carcinoma (FMTC) due to a RET V804M (GTG-->ATG) mutation. | Feldman GL | Surgery | 2000 | PMID: 10876191 |
A RET double mutation in the germline of a kindred with FMTC. | Bartsch DK | Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association | 2000 | PMID: 10826520 |
A two-hit model for development of multiple endocrine neoplasia type 2B by RET mutations. | Iwashita T | Biochemical and biophysical research communications | 2000 | PMID: 10679286 |
Two germline missense mutations at codons 804 and 806 of the RET proto-oncogene in the same allele in a patient with multiple endocrine neoplasia type 2B without codon 918 mutation. | Miyauchi A | Japanese journal of cancer research : Gann | 1999 | PMID: 10076558 |
Prophylactic thyroidectomy in 75 children and adolescents with hereditary medullary thyroid carcinoma: German and Austrian experience. | Dralle H | World journal of surgery | 1998 | PMID: 9606292 |
A GTG to ATG novel point mutation at codon 804 in exon 14 of the RET proto-oncogene in two families affected by familial medullary thyroid carcinoma. | Fattoruso O | Human mutation | 1998 | PMID: 9452077 |
Distinction between sporadic and hereditary medullary thyroid carcinoma (MTC) by mutation analysis of the RET proto-oncogene. "Study Group Multiple Endocrine Neoplasia Austria (SMENA)". | Fink M | International journal of cancer | 1996 | PMID: 8797874 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RET | - | - | - | - |
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Text-mined citations for this variant ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.