NM_020975.6(RET):c.2611G>A (p.Val871Ile) AND Multiple endocrine neoplasia, type 2

Clinical significance:Uncertain significance (Last evaluated: Nov 2, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000123312.8

Allele description [Variation Report for NM_020975.6(RET):c.2611G>A (p.Val871Ile)]

NM_020975.6(RET):c.2611G>A (p.Val871Ile)

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.2611G>A (p.Val871Ile)
HGVS:
  • NC_000010.11:g.43120084G>A
  • NG_007489.1:g.48016G>A
  • NM_001355216.1:c.1849G>A
  • NM_020630.6:c.2611G>A
  • NM_020975.6:c.2611G>AMANE SELECT
  • NP_001342145.1:p.Val617Ile
  • NP_065681.1:p.Val871Ile
  • NP_066124.1:p.Val871Ile
  • NP_066124.1:p.Val871Ile
  • LRG_518t1:c.2611G>A
  • LRG_518t2:c.2611G>A
  • LRG_518:g.48016G>A
  • LRG_518p1:p.Val871Ile
  • NC_000010.10:g.43615532G>A
  • NM_020630.4:c.2611G>A
  • NM_020975.4:c.2611G>A
Protein change:
V617I
Links:
dbSNP: rs145170911
NCBI 1000 Genomes Browser:
rs145170911
Molecular consequence:
  • NM_001355216.1:c.1849G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020630.6:c.2611G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020975.6:c.2611G>A - 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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000166619Invitaecriteria provided, single submitter
Uncertain significance
(Nov 2, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Twenty-Five Years Experience on RET Genetic Screening on Hereditary MTC: An Update on The Prevalence of Germline RET Mutations.

Elisei R, Tacito A, Ramone T, Ciampi R, Bottici V, Cappagli V, Viola D, Matrone A, Lorusso L, Valerio L, Giani C, Campopiano C, Prete A, Agate L, Molinaro E, Romei C.

Genes (Basel). 2019 Sep 10;10(9). doi:pii: E698. 10.3390/genes10090698.

PubMed [citation]
PMID:
31510104
PMCID:
PMC6771015

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000166619.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces valine with isoleucine at codon 871 of the RET protein (p.Val871Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs145170911, ExAC 0.04%). This variant has been reported in an individual affected with medullary thyroid carcinoma (PMID: 31510104). ClinVar contains an entry for this variant (Variation ID: 41842). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). 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.

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

Last Updated: Nov 20, 2021

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