NM_020975.6(RET):c.2432C>G (p.Ser811Cys) AND Multiple endocrine neoplasia, type 2

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 23, 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:: RCV000808281.9

Allele description

NM_020975.6(RET):c.2432C>G (p.Ser811Cys)

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.2432C>G (p.Ser811Cys)

HGVS:

NC_000010.11:g.43119570C>G
NG_007489.1:g.47502C>G
NM_000323.2:c.2432C>G
NM_001355216.2:c.1670C>G
NM_001406743.1:c.2432C>G
NM_001406744.1:c.2432C>G
NM_001406759.1:c.2432C>G
NM_001406760.1:c.2432C>G
NM_001406761.1:c.2303C>G
NM_001406762.1:c.2303C>G
NM_001406763.1:c.2297C>G
NM_001406764.1:c.2303C>G
NM_001406765.1:c.2297C>G
NM_001406766.1:c.2144C>G
NM_001406767.1:c.2144C>G
NM_001406768.1:c.2168C>G
NM_001406769.1:c.2036C>G
NM_001406770.1:c.2144C>G
NM_001406771.1:c.1994C>G
NM_001406772.1:c.2036C>G
NM_001406773.1:c.1994C>G
NM_001406774.1:c.1907C>G
NM_001406775.1:c.1706C>G
NM_001406776.1:c.1706C>G
NM_001406777.1:c.1706C>G
NM_001406778.1:c.1706C>G
NM_001406779.1:c.1535C>G
NM_001406780.1:c.1535C>G
NM_001406781.1:c.1535C>G
NM_001406782.1:c.1535C>G
NM_001406783.1:c.1406C>G
NM_001406784.1:c.1442C>G
NM_001406785.1:c.1415C>G
NM_001406786.1:c.1406C>G
NM_001406787.1:c.1400C>G
NM_001406788.1:c.1247C>G
NM_001406789.1:c.1247C>G
NM_001406790.1:c.1247C>G
NM_001406791.1:c.1127C>G
NM_001406792.1:c.983C>G
NM_001406793.1:c.983C>G
NM_001406794.1:c.983C>G
NM_020629.2:c.2432C>G
NM_020630.7:c.2432C>G
NM_020975.6:c.2432C>GMANE SELECT
NP_000314.1:p.Ser811Cys
NP_001342145.1:p.Ser557Cys
NP_001342145.1:p.Ser557Cys
NP_001393672.1:p.Ser811Cys
NP_001393673.1:p.Ser811Cys
NP_001393688.1:p.Ser811Cys
NP_001393689.1:p.Ser811Cys
NP_001393690.1:p.Ser768Cys
NP_001393691.1:p.Ser768Cys
NP_001393692.1:p.Ser766Cys
NP_001393693.1:p.Ser768Cys
NP_001393694.1:p.Ser766Cys
NP_001393695.1:p.Ser715Cys
NP_001393696.1:p.Ser715Cys
NP_001393697.1:p.Ser723Cys
NP_001393698.1:p.Ser679Cys
NP_001393699.1:p.Ser715Cys
NP_001393700.1:p.Ser665Cys
NP_001393701.1:p.Ser679Cys
NP_001393702.1:p.Ser665Cys
NP_001393703.1:p.Ser636Cys
NP_001393704.1:p.Ser569Cys
NP_001393705.1:p.Ser569Cys
NP_001393706.1:p.Ser569Cys
NP_001393707.1:p.Ser569Cys
NP_001393708.1:p.Ser512Cys
NP_001393709.1:p.Ser512Cys
NP_001393710.1:p.Ser512Cys
NP_001393711.1:p.Ser512Cys
NP_001393712.1:p.Ser469Cys
NP_001393713.1:p.Ser481Cys
NP_001393714.1:p.Ser472Cys
NP_001393715.1:p.Ser469Cys
NP_001393716.1:p.Ser467Cys
NP_001393717.1:p.Ser416Cys
NP_001393718.1:p.Ser416Cys
NP_001393719.1:p.Ser416Cys
NP_001393720.1:p.Ser376Cys
NP_001393721.1:p.Ser328Cys
NP_001393722.1:p.Ser328Cys
NP_001393723.1:p.Ser328Cys
NP_065680.1:p.Ser811Cys
NP_065681.1:p.Ser811Cys
NP_065681.1:p.Ser811Cys
NP_065681.1:p.Ser811Cys
NP_066124.1:p.Ser811Cys
NP_066124.1:p.Ser811Cys
LRG_518t1:c.2432C>G
LRG_518t2:c.2432C>G
LRG_518:g.47502C>G
LRG_518p1:p.Ser811Cys
LRG_518p2:p.Ser811Cys
NC_000010.10:g.43615018C>G
NM_001355216.1:c.1670C>G
NM_020630.4:c.2432C>G
NM_020630.6:c.2432C>G
NM_020975.4:c.2432C>G

Protein change:

S328C

Links:

dbSNP: rs587778657

NCBI 1000 Genomes Browser:

rs587778657

Molecular consequence:

NM_000323.2:c.2432C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001355216.2:c.1670C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406743.1:c.2432C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406744.1:c.2432C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406759.1:c.2432C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406760.1:c.2432C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406761.1:c.2303C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406762.1:c.2303C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406763.1:c.2297C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406764.1:c.2303C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406765.1:c.2297C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406766.1:c.2144C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406767.1:c.2144C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406768.1:c.2168C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406769.1:c.2036C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406770.1:c.2144C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406771.1:c.1994C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406772.1:c.2036C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406773.1:c.1994C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406774.1:c.1907C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406775.1:c.1706C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406776.1:c.1706C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406777.1:c.1706C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406778.1:c.1706C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406779.1:c.1535C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406780.1:c.1535C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406781.1:c.1535C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406782.1:c.1535C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406783.1:c.1406C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406784.1:c.1442C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406785.1:c.1415C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406786.1:c.1406C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406787.1:c.1400C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406788.1:c.1247C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406789.1:c.1247C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406790.1:c.1247C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406791.1:c.1127C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406792.1:c.983C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406793.1:c.983C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406794.1:c.983C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_020629.2:c.2432C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_020630.7:c.2432C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_020975.6:c.2432C>G - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000948383	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 23, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000948383

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 23, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000948383.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

ClinVar contains an entry for this variant (Variation ID: 135179). 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 disruptive. 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. This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 811 of the RET protein (p.Ser811Cys).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 2, 2024

ClinVar

Relating variation to medicine