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NM_020975.6(RET):c.1903C>T (p.Arg635Cys) AND Multiple endocrine neoplasia, type 2

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 3, 2023
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:
RCV000531061.16

Allele description [Variation Report for NM_020975.6(RET):c.1903C>T (p.Arg635Cys)]

NM_020975.6(RET):c.1903C>T (p.Arg635Cys)

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.1903C>T (p.Arg635Cys)
HGVS:
  • NC_000010.11:g.43114503C>T
  • NG_007489.1:g.42435C>T
  • NM_000323.2:c.1903C>T
  • NM_001355216.2:c.1141C>T
  • NM_001406743.1:c.1903C>T
  • NM_001406744.1:c.1903C>T
  • NM_001406759.1:c.1903C>T
  • NM_001406760.1:c.1903C>T
  • NM_001406761.1:c.1774C>T
  • NM_001406762.1:c.1774C>T
  • NM_001406764.1:c.1774C>T
  • NM_001406766.1:c.1615C>T
  • NM_001406767.1:c.1615C>T
  • NM_001406769.1:c.1507C>T
  • NM_001406770.1:c.1615C>T
  • NM_001406771.1:c.1465C>T
  • NM_001406772.1:c.1507C>T
  • NM_001406773.1:c.1465C>T
  • NM_001406774.1:c.1378C>T
  • NM_001406775.1:c.1177C>T
  • NM_001406776.1:c.1177C>T
  • NM_001406777.1:c.1177C>T
  • NM_001406778.1:c.1177C>T
  • NM_001406779.1:c.1006C>T
  • NM_001406780.1:c.1006C>T
  • NM_001406781.1:c.1006C>T
  • NM_001406782.1:c.1006C>T
  • NM_001406783.1:c.877C>T
  • NM_001406784.1:c.913C>T
  • NM_001406785.1:c.886C>T
  • NM_001406786.1:c.877C>T
  • NM_001406788.1:c.718C>T
  • NM_001406789.1:c.718C>T
  • NM_001406790.1:c.718C>T
  • NM_001406791.1:c.598C>T
  • NM_001406792.1:c.454C>T
  • NM_001406793.1:c.454C>T
  • NM_001406794.1:c.454C>T
  • NM_020629.2:c.1903C>T
  • NM_020630.7:c.1903C>T
  • NM_020975.6:c.1903C>TMANE SELECT
  • NP_000314.1:p.Arg635Cys
  • NP_001342145.1:p.Arg381Cys
  • NP_001342145.1:p.Arg381Cys
  • NP_001393672.1:p.Arg635Cys
  • NP_001393673.1:p.Arg635Cys
  • NP_001393688.1:p.Arg635Cys
  • NP_001393689.1:p.Arg635Cys
  • NP_001393690.1:p.Arg592Cys
  • NP_001393691.1:p.Arg592Cys
  • NP_001393693.1:p.Arg592Cys
  • NP_001393695.1:p.Arg539Cys
  • NP_001393696.1:p.Arg539Cys
  • NP_001393698.1:p.Arg503Cys
  • NP_001393699.1:p.Arg539Cys
  • NP_001393700.1:p.Arg489Cys
  • NP_001393701.1:p.Arg503Cys
  • NP_001393702.1:p.Arg489Cys
  • NP_001393703.1:p.Arg460Cys
  • NP_001393704.1:p.Arg393Cys
  • NP_001393705.1:p.Arg393Cys
  • NP_001393706.1:p.Arg393Cys
  • NP_001393707.1:p.Arg393Cys
  • NP_001393708.1:p.Arg336Cys
  • NP_001393709.1:p.Arg336Cys
  • NP_001393710.1:p.Arg336Cys
  • NP_001393711.1:p.Arg336Cys
  • NP_001393712.1:p.Arg293Cys
  • NP_001393713.1:p.Arg305Cys
  • NP_001393714.1:p.Arg296Cys
  • NP_001393715.1:p.Arg293Cys
  • NP_001393717.1:p.Arg240Cys
  • NP_001393718.1:p.Arg240Cys
  • NP_001393719.1:p.Arg240Cys
  • NP_001393720.1:p.Arg200Cys
  • NP_001393721.1:p.Arg152Cys
  • NP_001393722.1:p.Arg152Cys
  • NP_001393723.1:p.Arg152Cys
  • NP_065680.1:p.Arg635Cys
  • NP_065681.1:p.Arg635Cys
  • NP_065681.1:p.Arg635Cys
  • NP_065681.1:p.Arg635Cys
  • NP_066124.1:p.Arg635Cys
  • NP_066124.1:p.Arg635Cys
  • LRG_518t1:c.1903C>T
  • LRG_518t2:c.1903C>T
  • LRG_518:g.42435C>T
  • LRG_518p1:p.Arg635Cys
  • LRG_518p2:p.Arg635Cys
  • NC_000010.10:g.43609951C>T
  • NM_001355216.1:c.1141C>T
  • NM_020630.4:c.1903C>T
  • NM_020630.6:c.1903C>T
  • NM_020975.4:c.1903C>T
Protein change:
R152C
Links:
dbSNP: rs377767410
NCBI 1000 Genomes Browser:
rs377767410
Molecular consequence:
  • NM_000323.2:c.1903C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001355216.2:c.1141C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406743.1:c.1903C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406744.1:c.1903C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406759.1:c.1903C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406760.1:c.1903C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406761.1:c.1774C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406762.1:c.1774C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406764.1:c.1774C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406766.1:c.1615C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406767.1:c.1615C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406769.1:c.1507C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406770.1:c.1615C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406771.1:c.1465C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406772.1:c.1507C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406773.1:c.1465C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406774.1:c.1378C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406775.1:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406776.1:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406777.1:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406778.1:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406779.1:c.1006C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406780.1:c.1006C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406781.1:c.1006C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406782.1:c.1006C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406783.1:c.877C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406784.1:c.913C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406785.1:c.886C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406786.1:c.877C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406788.1:c.718C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406789.1:c.718C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406790.1:c.718C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406791.1:c.598C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406792.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406793.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406794.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020629.2:c.1903C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020630.7:c.1903C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020975.6:c.1903C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Multiple endocrine neoplasia, type 2 (MEN2)
Identifiers:
MONDO: MONDO:0019003; MedGen: C4048306

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000658428Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 3, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

A patient with an apparently sporadic pheochromocytoma with a rearranged during transfection codon 635 variant: a mild form of multiple endocrine neoplasia type 2?

Huguet I, Cranston T, Walker L, Karavitaki N, Grossman AB.

Endocr Pract. 2014 Apr;20(4):e65-8. doi: 10.4158/EP13424.CR.

PubMed [citation]
PMID:
24449676

Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract.

Heidet L, Morinière V, Henry C, De Tomasi L, Reilly ML, Humbert C, Alibeu O, Fourrage C, Bole-Feysot C, Nitschké P, Tores F, Bras M, Jeanpierre M, Pietrement C, Gaillard D, Gonzales M, Novo R, Schaefer E, Roume J, Martinovic J, Malan V, Salomon R, et al.

J Am Soc Nephrol. 2017 Oct;28(10):2901-2914. doi: 10.1681/ASN.2017010043. Epub 2017 May 31.

PubMed [citation]
PMID:
28566479
PMCID:
PMC5619971
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000658428.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 477333). This missense change has been observed in individual(s) with congenital anomalies of the kidney and urinary tract and pheochromocytoma (PMID: 24449676, 28566479). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 635 of the RET protein (p.Arg635Cys).

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

Last Updated: May 1, 2024