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NM_020975.6(RET):c.1900T>G (p.Cys634Gly) AND MEN2 phenotype: Unclassified

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 25, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001420921.2

Allele description [Variation Report for NM_020975.6(RET):c.1900T>G (p.Cys634Gly)]

NM_020975.6(RET):c.1900T>G (p.Cys634Gly)

Gene:
RET:ret proto-oncogene [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q11.21
Genomic location:
Preferred name:
NM_020975.6(RET):c.1900T>G (p.Cys634Gly)
Other names:
p.C634G:TGC>GGC
HGVS:
  • NC_000010.11:g.43114500T>G
  • NG_007489.1:g.42432T>G
  • NM_000323.2:c.1900T>G
  • NM_001355216.2:c.1138T>G
  • NM_001406743.1:c.1900T>G
  • NM_001406744.1:c.1900T>G
  • NM_001406759.1:c.1900T>G
  • NM_001406760.1:c.1900T>G
  • NM_001406761.1:c.1771T>G
  • NM_001406762.1:c.1771T>G
  • NM_001406764.1:c.1771T>G
  • NM_001406766.1:c.1612T>G
  • NM_001406767.1:c.1612T>G
  • NM_001406769.1:c.1504T>G
  • NM_001406770.1:c.1612T>G
  • NM_001406771.1:c.1462T>G
  • NM_001406772.1:c.1504T>G
  • NM_001406773.1:c.1462T>G
  • NM_001406774.1:c.1375T>G
  • NM_001406775.1:c.1174T>G
  • NM_001406776.1:c.1174T>G
  • NM_001406777.1:c.1174T>G
  • NM_001406778.1:c.1174T>G
  • NM_001406779.1:c.1003T>G
  • NM_001406780.1:c.1003T>G
  • NM_001406781.1:c.1003T>G
  • NM_001406782.1:c.1003T>G
  • NM_001406783.1:c.874T>G
  • NM_001406784.1:c.910T>G
  • NM_001406785.1:c.883T>G
  • NM_001406786.1:c.874T>G
  • NM_001406788.1:c.715T>G
  • NM_001406789.1:c.715T>G
  • NM_001406790.1:c.715T>G
  • NM_001406791.1:c.595T>G
  • NM_001406792.1:c.451T>G
  • NM_001406793.1:c.451T>G
  • NM_001406794.1:c.451T>G
  • NM_020629.2:c.1900T>G
  • NM_020630.7:c.1900T>G
  • NM_020975.6:c.1900T>GMANE SELECT
  • NP_000314.1:p.Cys634Gly
  • NP_001342145.1:p.Cys380Gly
  • NP_001342145.1:p.Cys380Gly
  • NP_001393672.1:p.Cys634Gly
  • NP_001393673.1:p.Cys634Gly
  • NP_001393688.1:p.Cys634Gly
  • NP_001393689.1:p.Cys634Gly
  • NP_001393690.1:p.Cys591Gly
  • NP_001393691.1:p.Cys591Gly
  • NP_001393693.1:p.Cys591Gly
  • NP_001393695.1:p.Cys538Gly
  • NP_001393696.1:p.Cys538Gly
  • NP_001393698.1:p.Cys502Gly
  • NP_001393699.1:p.Cys538Gly
  • NP_001393700.1:p.Cys488Gly
  • NP_001393701.1:p.Cys502Gly
  • NP_001393702.1:p.Cys488Gly
  • NP_001393703.1:p.Cys459Gly
  • NP_001393704.1:p.Cys392Gly
  • NP_001393705.1:p.Cys392Gly
  • NP_001393706.1:p.Cys392Gly
  • NP_001393707.1:p.Cys392Gly
  • NP_001393708.1:p.Cys335Gly
  • NP_001393709.1:p.Cys335Gly
  • NP_001393710.1:p.Cys335Gly
  • NP_001393711.1:p.Cys335Gly
  • NP_001393712.1:p.Cys292Gly
  • NP_001393713.1:p.Cys304Gly
  • NP_001393714.1:p.Cys295Gly
  • NP_001393715.1:p.Cys292Gly
  • NP_001393717.1:p.Cys239Gly
  • NP_001393718.1:p.Cys239Gly
  • NP_001393719.1:p.Cys239Gly
  • NP_001393720.1:p.Cys199Gly
  • NP_001393721.1:p.Cys151Gly
  • NP_001393722.1:p.Cys151Gly
  • NP_001393723.1:p.Cys151Gly
  • NP_065680.1:p.Cys634Gly
  • NP_065681.1:p.Cys634Gly
  • NP_065681.1:p.Cys634Gly
  • NP_065681.1:p.Cys634Gly
  • NP_066124.1:p.Cys634Gly
  • NP_066124.1:p.Cys634Gly
  • LRG_518t1:c.1900T>G
  • LRG_518t2:c.1900T>G
  • LRG_518:g.42432T>G
  • LRG_518p1:p.Cys634Gly
  • LRG_518p2:p.Cys634Gly
  • NC_000010.10:g.43609948T>G
  • NM_001355216.1:c.1138T>G
  • NM_020630.4:c.1900T>G
  • NM_020630.6:c.1900T>G
  • NM_020975.4:c.1900T>G
  • P07949:p.Cys634Gly
Protein change:
C151G; CYS634GLY
Links:
UniProtKB: P07949#VAR_006323; OMIM: 164761.0003; dbSNP: rs75076352
NCBI 1000 Genomes Browser:
rs75076352
Molecular consequence:
  • NM_000323.2:c.1900T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001355216.2:c.1138T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406743.1:c.1900T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406744.1:c.1900T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406759.1:c.1900T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406760.1:c.1900T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406761.1:c.1771T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406762.1:c.1771T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406764.1:c.1771T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406766.1:c.1612T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406767.1:c.1612T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406769.1:c.1504T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406770.1:c.1612T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406771.1:c.1462T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406772.1:c.1504T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406773.1:c.1462T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406774.1:c.1375T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406775.1:c.1174T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406776.1:c.1174T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406777.1:c.1174T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406778.1:c.1174T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406779.1:c.1003T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406780.1:c.1003T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406781.1:c.1003T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406782.1:c.1003T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406783.1:c.874T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406784.1:c.910T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406785.1:c.883T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406786.1:c.874T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406788.1:c.715T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406789.1:c.715T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406790.1:c.715T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406791.1:c.595T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406792.1:c.451T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406793.1:c.451T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406794.1:c.451T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020629.2:c.1900T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020630.7:c.1900T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020975.6:c.1900T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
MEN2 phenotype: Unclassified
Identifiers:
MedGen: CN311636

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001623374Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Apr 25, 2021) 		germlineclinical testing

PubMed (20)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Germ-line mutations in nonsyndromic pheochromocytoma.

Neumann HP, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Smith WM, Munk R, Manz T, Glaesker S, Apel TW, Treier M, Reineke M, Walz MK, Hoang-Vu C, Brauckhoff M, et al.

N Engl J Med. 2002 May 9;346(19):1459-66.

PubMed [citation]
PMID:
12000816

Clinical characteristics and genetic screening of an extended family with MEN2A.

Algün E, Abaci N, Kösem M, Kotan C, Köseoğlu B, Boztepe H, Sekeroğlu R, Aslan H, Topal C, Ayakta H, Uygan I, Alagöl F, Erginel-Unaltuna N, Aksoy H.

J Endocrinol Invest. 2002 Jul-Aug;25(7):603-8.

PubMed [citation]
PMID:
12150334
See all PubMed Citations (20)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001623374.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (20)

Description

Variant summary: RET c.1900T>G (p.Cys634Gly) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The most frequent mutations in the RET proto-oncogene have been found in five cysteine codons 609, 611, 618, and 620 of exon 10 and codon 634 of exon 11. The variant was absent in 247534 control chromosomes. c.1900T>G has been widely reported in the literature in multiple individuals affected with Multiple Endocrine Neoplasia Type 2/Phaeochromocytoma/Medullary Carcinoma of the Thyroid/ multiple endocrine neoplasia type 2A (MEN 2A)-cutaneous lichen amyloidosis (example, Mulligan_1993, Neumann_2002, Sanz_2009, Hedayati_2011, Qi_2018, Maciel_2019). These data indicate that the variant is very likely to be associated with disease. Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024