NM_020975.6(RET):c.235C>T (p.Arg79Trp) AND Multiple endocrine neoplasia, type 2

Clinical significance:Uncertain significance (Last evaluated: Oct 25, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000463969.6

Allele description [Variation Report for NM_020975.6(RET):c.235C>T (p.Arg79Trp)]

NM_020975.6(RET):c.235C>T (p.Arg79Trp)

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.235C>T (p.Arg79Trp)
HGVS:
  • NC_000010.11:g.43100620C>T
  • NG_007489.1:g.28552C>T
  • NM_020630.6:c.235C>T
  • NM_020975.6:c.235C>TMANE SELECT
  • NP_065681.1:p.Arg79Trp
  • NP_066124.1:p.Arg79Trp
  • LRG_518t1:c.235C>T
  • LRG_518:g.28552C>T
  • NC_000010.10:g.43596068C>T
  • NC_000010.10:g.43596068C>T
  • NM_020975.4:c.235C>T
Protein change:
R79W
Links:
dbSNP: rs537523906
NCBI 1000 Genomes Browser:
rs537523906
Molecular consequence:
  • NM_020630.6:c.235C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020975.6:c.235C>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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000543820Invitaecriteria provided, single submitter
Uncertain significance
(Oct 25, 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

RET and EDNRB mutation screening in patients with Hirschsprung disease: Functional studies and its implications for genetic counseling.

Widowati T, Melhem S, Patria SY, de Graaf BM, Sinke RJ, Viel M, Dijkhuis J, Sadewa AH, Purwohardjono R, Soenarto Y, Hofstra RM, Sribudiani Y.

Eur J Hum Genet. 2016 Jun;24(6):823-9. doi: 10.1038/ejhg.2015.214. Epub 2015 Sep 23.

PubMed [citation]
PMID:
26395553
PMCID:
PMC4867453

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, SCV000543820.6

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

Description

This sequence change replaces arginine with tryptophan at codon 79 of the RET protein (p.Arg79Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs537523906, ExAC 0.05%). This variant has been reported in an individual with Hirschsprung disease (PMID: 26395553). ClinVar contains an entry for this variant (Variation ID: 405541). An experimental study has shown that this missense change does not affect phosphorylation of the RET and ERK proteins compared to the wild-type RET protein (PMID: 26395553). 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: Oct 24, 2021

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