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NM_020975.6(RET):c.1901G>T (p.Cys634Phe)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
5 (Most recent: Nov 4, 2021)
Last evaluated:
Nov 3, 2021
Accession:
VCV000013911.6
Variation ID:
13911
Description:
single nucleotide variant
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NM_020975.6(RET):c.1901G>T (p.Cys634Phe)

Allele ID
28950
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
10q11.21
Genomic location
10: 43114501 (GRCh38) GRCh38 UCSC
10: 43609949 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P07949:p.Cys634Phe
LRG_518:g.42433G>T
LRG_518t2:c.1901G>T
... more HGVS
Protein change
C634F, C380F
Other names
-
Canonical SPDI
NC_000010.11:43114500:G:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00001
Links
ClinGen: CA008370
UniProtKB: P07949#VAR_006324
OMIM: 164761.0006
dbSNP: rs75996173
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 1 criteria provided, single submitter Mar 12, 2020 RCV000471652.7
Pathogenic 1 criteria provided, single submitter Nov 3, 2021 RCV001770038.1
Pathogenic 1 no assertion criteria provided May 9, 2002 RCV000014928.21
Pathogenic 1 no assertion criteria provided May 9, 2002 RCV000014930.21
Pathogenic 1 no assertion criteria provided May 9, 2002 RCV000014929.21
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
RET Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
1738 1809

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Mar 12, 2020)
criteria provided, single submitter
Method: clinical testing
Multiple endocrine neoplasia, type 2
Allele origin: germline
Invitae
Accession: SCV000543841.6
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (11)
Comment:
This sequence change replaces cysteine with phenylalanine at codon 634 of the RET protein (p.Cys634Phe). The cysteine residue is highly conserved and there is a … (more)
Pathogenic
(Nov 03, 2021)
criteria provided, single submitter
Method: clinical testing
Hirschsprung disease 1
Allele origin: germline
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002011457.1
Submitted: (Nov 04, 2021)
Evidence details
Pathogenic
(May 09, 2002)
no assertion criteria provided
Method: literature only
MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIA
Allele origin: germline
OMIM
Accession: SCV000035184.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (5)
Pathogenic
(May 09, 2002)
no assertion criteria provided
Method: literature only
THYROID CARCINOMA, FAMILIAL MEDULLARY
Allele origin: germline
OMIM
Accession: SCV000035185.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (5)
Pathogenic
(May 09, 2002)
no assertion criteria provided
Method: literature only
PHEOCHROMOCYTOMA
Allele origin: germline
OMIM
Accession: SCV000035186.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (5)

Functional evidence

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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 this variant

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Title Author Journal Year Link
Molecular diagnosis and comprehensive treatment of multiple endocrine neoplasia type 2 in Southeastern Chinese. Zhao JQ Hereditary cancer in clinical practice 2015 PMID: 25628771
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
Characterization of wild-type and mutated RET proto- oncogene associated with familial medullary thyroid cancer. Masbi MH Asian Pacific journal of cancer prevention : APJCP 2014 PMID: 24716929
Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple endocrine neoplasia type 2A mutation (codon 634). Jesić MD Srpski arhiv za celokupno lekarstvo 2014 PMID: 24684035
Predominant RET Germline Mutations in Exons 10, 11, and 16 in Iranian Patients with Hereditary Medullary Thyroid Carcinoma. Hedayati M Journal of thyroid research 2011 PMID: 21765987
Coincidence of multiple endocrine neoplasia type 2A with acromegaly. Saito T The American journal of the medical sciences 2010 PMID: 20739875
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
Genotype-phenotype correlations in Hungarian patients with hereditary medullary thyroid cancer. Patocs A Wiener klinische Wochenschrift 2006 PMID: 16865647
Germ-line mutations in nonsyndromic pheochromocytoma. Neumann HP The New England journal of medicine 2002 PMID: 12000816
Germline RET mutations in MEN 2A and FMTC and their detection by simple DNA diagnostic tests. Xue F Human molecular genetics 1994 PMID: 7915165
Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC. Mulligan LM Nature genetics 1994 PMID: 7907913
Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Mulligan LM Nature 1993 PMID: 8099202
Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains. Takahashi M Oncogene 1988 PMID: 3078962

Text-mined citations for rs75996173...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 20, 2021