chr10:43617416:T>C Detail (hg19) (RET)

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Summary
Information
Links
Disease area statistics
MGeND
ClinVar
CIViC
DisGeNET
Annotation
Genome browser

Information

Genome

Assembly	Position
hg19	chr10:43,617,416-43,617,416
hg38	chr10:43,121,968-43,121,968 View the variant detail on this assembly version.

HGVS

Type	Transcript	Protein
RefSeq	NM_020630.4:c.2753T>C	NP_065681.1:p.Met918Thr
	NM_020975.4:c.2753T>C	NP_066124.1:p.Met918Thr
Ensemble	ENST00000340058.6:c.2753T>C	ENST00000340058.6:p.Met918Thr
	ENST00000713926.1:c.2489T>C	ENST00000713926.1:p.Met830Thr
	ENST00000355710.8:c.2753T>C	ENST00000355710.8:p.Met918Thr
	ENST00000615310.5:c.2357T>C	ENST00000615310.5:p.Met786Thr

Summary

MGeND

Clinical significance
Variant entry
GWAS entry
Disease area statistics	Show details

Frequency

[No Data.]

Prediction

ClinVar

Clinical Significance	Pathogenic Likely pathogenic
Review star
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Links

Type	Database	ID	Link
Gene	MIM	164761	OMIM
	HGNC	9967	HGNC
	Ensembl	ENSG00000165731	Ensembl
	NCBI		NCBI
	Gene Cards		Gene Cards
	OncoKB		OncoKB

Type	Database	ID	Link
Variant	TogoVar
	COSMIC	COSM4770356	COSMIC
	MONDO

Disease area statistics

[No Data.]

MGeND

[No Data.]

ClinVar

Clinical significance	Last evaluated	Review status	Condition	Origin	Links
Pathogenic	2023-05-21	criteria provided, multiple submitters, no conflicts	multiple endocrine neoplasia type 2B	unknown de novo germline somatic	Detail
Pathogenic	1998-05-07	no assertion criteria provided	Thyroid carcinoma, sporadic medullary	unknown	Detail
Pathogenic	1998-05-07	no assertion criteria provided	pheochromocytoma	somatic	Detail
Pathogenic	2023-08-15	criteria provided, multiple submitters, no conflicts	not provided	germline	Detail
Pathogenic	2023-12-22	criteria provided, single submitter	Multiple endocrine neoplasia, type 2	germline	Detail
Pathogenic	2020-12-15	criteria provided, multiple submitters, no conflicts	multiple endocrine neoplasia type 2A	germline unknown somatic	Detail
Pathogenic	2014-12-08	criteria provided, single submitter	tetralogy of Fallot,Hypertelorism	unknown	Detail
Pathogenic	2014-12-08	criteria provided, single submitter	tetralogy of Fallot,Hypertelorism	unknown	Detail
Pathogenic	2017-08-02	criteria provided, single submitter	Medullary thyroid carcinoma	germline somatic	Detail
Likely pathogenic	2016-05-13	no assertion criteria provided	Multiple endocrine neoplasia, type 1	somatic	Detail
Pathogenic	2014-10-02	no assertion criteria provided	Thyroid tumor	somatic	Detail
Likely pathogenic	2016-05-13	no assertion criteria provided	multiple endocrine neoplasia type 4	somatic	Detail
Pathogenic	2019-04-16	criteria provided, single submitter	not specified	germline	Detail
Pathogenic	2022-12-23	criteria provided, multiple submitters, no conflicts	familial medullary thyroid carcinoma	de novo germline	Detail
Pathogenic Likely pathogenic	2024-03-29	criteria provided, multiple submitters, no conflicts	Hirschsprung disease, susceptibility to, 1	germline	Detail
Pathogenic	2022-03-11	criteria provided, multiple submitters, no conflicts	Hereditary cancer-predisposing syndrome	germline	Detail
Pathogenic	2024-02-21	criteria provided, single submitter	RET-related disorder	germline	Detail

CIViC

Disease	Drug	EL	ET	ED	CS	VO	TR	Pubmed	Links
thyroid gland medullary carcinoma	Sorafenib	B	Predictive	Supports	Sensitivity/Response	Somatic	3	20368568	Detail
thyroid gland medullary carcinoma		B	Diagnostic	Supports	Positive	Somatic	5	18073307	Detail
thyroid gland medullary carcinoma	Motesanib	D	Predictive	Supports	Resistance	Somatic	3	21422803	Detail
thyroid gland medullary carcinoma	JAK2 Inhibitor AZD1480	D	Predictive	Supports	Sensitivity/Response	Somatic	3	23056499	Detail
thyroid gland medullary carcinoma	Cabozantinib	B	Predictive	Supports	Sensitivity/Response	Somatic	4	27525386	Detail
thyroid gland medullary carcinoma		B	Prognostic	Supports	Poor Outcome	Somatic	4	9839497	Detail

DisGeNET

Score	Disease name	Description	Source	Pubmed	Links
0.320	Medullary carcinoma of thyroid	Multiple endocrine neoplasia type 2B with a RET proto-oncogene A883F mutation di...	BeFree	21186952	Detail
0.614	multiple endocrine neoplasia type 2A	Like RET with the M918T or A883F MEN 2B mutation, the transforming activity of R...	BeFree	10679286	Detail
0.592	multiple endocrine neoplasia type 2B	Multiple endocrine neoplasia type 2B with a RET proto-oncogene A883F mutation di...	BeFree	21186952	Detail
0.614	multiple endocrine neoplasia type 2A	NA	CLINVAR		Detail
0.592	multiple endocrine neoplasia type 2B	NA	CLINVAR		Detail
0.592	multiple endocrine neoplasia type 2B	Mutation analysis of exon 16 of the RET proto-oncogene revealed germline M918T a...	BeFree	10369718	Detail
<0.001	Ganglioneuromatosis	Early recognition of intestinal ganglioneuromatosis with germline RET M918T muta...	BeFree	10369718	Detail
0.614	multiple endocrine neoplasia type 2A	MEN2A (C618S), MEN2A/familial MTC (FMTC) (C620S), and MEN2B (M918T).	BeFree	22199277	Detail
<0.001	multiple endocrine neoplasia type 2B	In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nucl...	BeFree	15485908	Detail
0.592	multiple endocrine neoplasia type 2B	The hereditary multiple endocrine neoplasia syndromes types 2A and B (MEN 2A and...	BeFree	7559902	Detail
0.001	multiple endocrine neoplasia type 2B	A single RET mutation, resulting in the substitution M918T, has been identified ...	BeFree	9294615	Detail
0.605	pheochromocytoma	NA	CLINVAR		Detail
0.614	multiple endocrine neoplasia type 2A	The hereditary multiple endocrine neoplasia syndromes types 2A and B (MEN 2A and...	BeFree	7559902	Detail
0.001	Medullary carcinoma of thyroid	We assessed by immunohistochemistry the expression of EGFR, KIT, MET, PDGFRB, VE...	BeFree	24754736	Detail
0.320	Medullary carcinoma of thyroid	We assessed by immunohistochemistry the expression of EGFR, KIT, MET, PDGFRB, VE...	BeFree	24754736	Detail
<0.001	Medullary carcinoma of thyroid	In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nucl...	BeFree	15485908	Detail
0.592	multiple endocrine neoplasia type 2B	Renal aplasia in humans is associated with RET mutations.	UNIPROT	18252215	Detail
0.592	multiple endocrine neoplasia type 2B	Analysis of the RET protooncogene exons 10, 11, and 16 did not demonstrate point...	BeFree	9270546	Detail
0.592	multiple endocrine neoplasia type 2B	Single oligoarray-based detection of specific M918T mutation in RET oncogene in ...	BeFree	21253810	Detail
0.592	multiple endocrine neoplasia type 2B	More than 50% of patients with typical MEN-2B have a de novo M918T germline muta...	BeFree	15517484	Detail
0.005	Secondary malignant neoplasm of lymph node	In the present work, a comparative genomic hybridization (CGH) study was perform...	BeFree	22676344	Detail
0.592	multiple endocrine neoplasia type 2B	Although there were no syndromic features or a positive family history, mutation...	BeFree	16808642	Detail
0.320	Medullary carcinoma of thyroid	In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nucl...	BeFree	15485908	Detail
0.614	multiple endocrine neoplasia type 2A	RET harboring the mutations C634R (MEN 2A) or M918T (MEN 2B), in contrast to wil...	BeFree	11389085	Detail
<0.001	multiple endocrine neoplasia	In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nucl...	BeFree	15485908	Detail
0.305	multiple endocrine neoplasia	The hereditary multiple endocrine neoplasia syndromes types 2A and B (MEN 2A and...	BeFree	7559902	Detail
<0.001	Medullary carcinoma of thyroid	In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nucl...	BeFree	15485908	Detail
0.592	multiple endocrine neoplasia type 2B	Detailed information was gathered regarding the development of MEN 2B-associated...	BeFree	19041016	Detail
0.592	multiple endocrine neoplasia type 2B	In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nucl...	BeFree	15485908	Detail
0.320	Medullary carcinoma of thyroid	Until the end of the study, at a median age of 16.2 (range, 0.5-34.9 years), all...	BeFree	19041016	Detail
0.305	multiple endocrine neoplasia	In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nucl...	BeFree	15485908	Detail
<0.001	multiple endocrine neoplasia type 2B	In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nucl...	BeFree	15485908	Detail
0.592	multiple endocrine neoplasia type 2B	Forty-four MEN 2B patients carrying inherited (3 patients) and de novo (41 patie...	BeFree	23979292	Detail
0.109	Thyroid carcinoma	CGH alterations in medullary thyroid carcinomas in relation to the RET M918T mut...	BeFree	11351254	Detail
0.592	multiple endocrine neoplasia type 2B	RET harboring the mutations C634R (MEN 2A) or M918T (MEN 2B), in contrast to wil...	BeFree	11389085	Detail
0.001	multiple endocrine neoplasia type 2B	A single RET mutation, resulting in the substitution M918T, has been identified ...	BeFree	9294615	Detail
0.592	multiple endocrine neoplasia type 2B	MEN2A (C618S), MEN2A/familial MTC (FMTC) (C620S), and MEN2B (M918T).	BeFree	22199277	Detail
<0.001	multiple endocrine neoplasia	In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nucl...	BeFree	15485908	Detail
0.320	Medullary carcinoma of thyroid	Low prevalence of the somatic M918T RET mutation in micro-medullary thyroid canc...	BeFree	22404432	Detail
0.320	Medullary carcinoma of thyroid	The ensuing molecular genetic analysis revealed a M918T mutation of the RET prot...	BeFree	17848262	Detail
0.522	familial medullary thyroid carcinoma	Renal aplasia in humans is associated with RET mutations.	UNIPROT	18252215	Detail

Annotation

Annotations

Descrption	Source	Links
In a phase 2 clinical trial of sorafenib in patients with hereditary or sporadic advanced medullary ...	CIViC Evidence	Detail
In patients with medullary carcinoma, the presence of RET M918T mutation is associated with increase...	CIViC Evidence	Detail
Medullary thyroid cancer cells with RET M918T mutation are insensitive to motesanib, compared to wil...	CIViC Evidence	Detail
The use of AZD1480 on RET-mutated/rearranged cell lines in vitro led to strong repression of tyroid ...	CIViC Evidence	Detail
Cabozantinib significantly prolonged progression-free survival (PFS) versus placebo in patients with...	CIViC Evidence	Detail
Compared to those who harbor a wild type RET, patients with RET M918T mutation develop larger and mo...	CIViC Evidence	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND Multiple endocrine neoplasia type 2B	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND Thyroid carcinoma, sporadic medullary	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND Pheochromocytoma	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND not provided	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND Multiple endocrine neoplasia, type 2	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND Multiple endocrine neoplasia type 2A	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND multiple conditions	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND multiple conditions	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND Medullary thyroid carcinoma	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND Multiple endocrine neoplasia, type 1	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND Thyroid tumor	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND Multiple endocrine neoplasia type 4	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND not specified	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND Familial medullary thyroid carcinoma	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND Hirschsprung disease, susceptibility to, 1	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND Hereditary cancer-predisposing syndrome	ClinVar	Detail
NM_020975.6(RET):c.2753T>C (p.Met918Thr) AND RET-related disorder	ClinVar	Detail
Multiple endocrine neoplasia type 2B with a RET proto-oncogene A883F mutation displays a more indole...	DisGeNET	Detail
Like RET with the M918T or A883F MEN 2B mutation, the transforming activity of RET with the V804M/Y8...	DisGeNET	Detail
Multiple endocrine neoplasia type 2B with a RET proto-oncogene A883F mutation displays a more indole...	DisGeNET	Detail
NA	DisGeNET	Detail
NA	DisGeNET	Detail
Mutation analysis of exon 16 of the RET proto-oncogene revealed germline M918T and thus, a molecular...	DisGeNET	Detail
Early recognition of intestinal ganglioneuromatosis with germline RET M918T mutation in pseudo-Hirsc...	DisGeNET	Detail
MEN2A (C618S), MEN2A/familial MTC (FMTC) (C620S), and MEN2B (M918T).	DisGeNET	Detail
In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nuclear enrichment of ST...	DisGeNET	Detail
The hereditary multiple endocrine neoplasia syndromes types 2A and B (MEN 2A and B) were recently li...	DisGeNET	Detail
A single RET mutation, resulting in the substitution M918T, has been identified in 94% of cases of M...	DisGeNET	Detail
NA	DisGeNET	Detail
The hereditary multiple endocrine neoplasia syndromes types 2A and B (MEN 2A and B) were recently li...	DisGeNET	Detail
We assessed by immunohistochemistry the expression of EGFR, KIT, MET, PDGFRB, VEGF, VEGFR1, VEGFR2, ...	DisGeNET	Detail
We assessed by immunohistochemistry the expression of EGFR, KIT, MET, PDGFRB, VEGF, VEGFR1, VEGFR2, ...	DisGeNET	Detail
In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nuclear enrichment of ST...	DisGeNET	Detail
Renal aplasia in humans is associated with RET mutations.	DisGeNET	Detail
Analysis of the RET protooncogene exons 10, 11, and 16 did not demonstrate point mutation in the MEN...	DisGeNET	Detail
Single oligoarray-based detection of specific M918T mutation in RET oncogene in multiple endocrine n...	DisGeNET	Detail
More than 50% of patients with typical MEN-2B have a de novo M918T germline mutation of the RET prot...	DisGeNET	Detail
In the present work, a comparative genomic hybridization (CGH) study was performed using DNA from a ...	DisGeNET	Detail
Although there were no syndromic features or a positive family history, mutation analysis of the RET...	DisGeNET	Detail
In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nuclear enrichment of ST...	DisGeNET	Detail
RET harboring the mutations C634R (MEN 2A) or M918T (MEN 2B), in contrast to wild-type RET, activate...	DisGeNET	Detail
In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nuclear enrichment of ST...	DisGeNET	Detail
The hereditary multiple endocrine neoplasia syndromes types 2A and B (MEN 2A and B) were recently li...	DisGeNET	Detail
In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nuclear enrichment of ST...	DisGeNET	Detail
Detailed information was gathered regarding the development of MEN 2B-associated symptoms from the p...	DisGeNET	Detail
In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nuclear enrichment of ST...	DisGeNET	Detail
Until the end of the study, at a median age of 16.2 (range, 0.5-34.9 years), all 25 M918T RET carrie...	DisGeNET	Detail
In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nuclear enrichment of ST...	DisGeNET	Detail
In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nuclear enrichment of ST...	DisGeNET	Detail
Forty-four MEN 2B patients carrying inherited (3 patients) and de novo (41 patients) M918T RET mutat...	DisGeNET	Detail
CGH alterations in medullary thyroid carcinomas in relation to the RET M918T mutation and clinical o...	DisGeNET	Detail
RET harboring the mutations C634R (MEN 2A) or M918T (MEN 2B), in contrast to wild-type RET, activate...	DisGeNET	Detail
A single RET mutation, resulting in the substitution M918T, has been identified in 94% of cases of M...	DisGeNET	Detail
MEN2A (C618S), MEN2A/familial MTC (FMTC) (C620S), and MEN2B (M918T).	DisGeNET	Detail
In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nuclear enrichment of ST...	DisGeNET	Detail
Low prevalence of the somatic M918T RET mutation in micro-medullary thyroid cancer.	DisGeNET	Detail
The ensuing molecular genetic analysis revealed a M918T mutation of the RET protooncogene, which is ...	DisGeNET	Detail
Renal aplasia in humans is associated with RET mutations.	DisGeNET	Detail

Overlapped Transcript Coordinates

Gene	Transcript ID	Exon Number	Chromosome	Start	Stop	Type	Amino Mutation	Transcript Position	Links

Overlapped Transcript

Gene	Transcript ID	Chromosome	Start	Stop	Links

Gene: -
dbSNP: rs74799832 dbSNP
Genome: hg19
Position: chr10:43,617,416-43,617,416
Variant Type: snv
Reference Allele: T
Alternative Allele: C
Variant (CIViC) (CIViC Variant): M918T
Transcript 1 (CIViC Variant): ENST00000355710.3
Variant URL (CIViC Variant): https://civic.genome.wustl.edu/links/variants/113
Summary (CIViC Variant): RET M819T is the most common somatically acquired mutation in medullary thyroid cancer (MTC). While there currently are no RET-specific inhibiting agents, promiscuous kinase inhibitors have seen some success in treating RET overactivity. Data suggests however, that the M918T mutation may lead to drug resistance, especially against the VEGFR-inhibitor motesanib. It has also been suggested that RET M819T leads to more aggressive MTC with a poorer prognosis.

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