NM_020975.6(RET):c.938G>A (p.Arg313Gln) AND Multiple endocrine neoplasia, type 2

Clinical significance:Uncertain significance (Last evaluated: Dec 7, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000654592.2

Allele description [Variation Report for NM_020975.6(RET):c.938G>A (p.Arg313Gln)]

NM_020975.6(RET):c.938G>A (p.Arg313Gln)

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.938G>A (p.Arg313Gln)
HGVS:
  • NC_000010.11:g.43106446G>A
  • NG_007489.1:g.34378G>A
  • NM_001355216.1:c.176G>A
  • NM_020630.6:c.938G>A
  • NM_020975.6:c.938G>AMANE SELECT
  • NP_001342145.1:p.Arg59Gln
  • NP_065681.1:p.Arg313Gln
  • NP_066124.1:p.Arg313Gln
  • LRG_518t1:c.938G>A
  • LRG_518:g.34378G>A
  • NC_000010.10:g.43601894G>A
  • NM_020975.4:c.938G>A
  • P07949:p.Arg313Gln
Protein change:
R313Q; ARG313GLN
Links:
UniProtKB: P07949#VAR_009465; OMIM: 164761.0028; dbSNP: rs77702891
NCBI 1000 Genomes Browser:
rs77702891
Molecular consequence:
  • NM_001355216.1:c.176G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020630.6:c.938G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020975.6:c.938G>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
SCV000776486Invitaecriteria provided, single submitter
Uncertain significance
(Dec 7, 2018)
germlineclinical testing

PubMed (3)
[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 mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients.

So MT, Leon TY, Cheng G, Tang CS, Miao XP, Cornes BK, Diem NN, Cui L, Ngan ES, Lui VC, Wu XZ, Wang B, Wang H, Yuan ZW, Huang LM, Li L, Xia H, Zhu D, Liu J, Nguyen TL, Chan IH, Chung PH, et al.

PLoS One. 2011;6(12):e28986. doi: 10.1371/journal.pone.0028986. Epub 2011 Dec 9.

PubMed [citation]
PMID:
22174939
PMCID:
PMC3235168

Frequency of RET mutations in long- and short-segment Hirschsprung disease.

Seri M, Yin L, Barone V, Bolino A, Celli I, Bocciardi R, Pasini B, Ceccherini I, Lerone M, Kristoffersson U, Larsson LT, Casasa JM, Cass DT, Abramowicz MJ, Vanderwinden JM, Kravcenkiene I, Baric I, Silengo M, Martucciello G, Romeo G.

Hum Mutat. 1997;9(3):243-9.

PubMed [citation]
PMID:
9090527
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000776486.2

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

Description

This sequence change replaces arginine with glutamine at codon 313 of the RET protein (p.Arg313Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs77702891, ExAC 0.1%) and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in individuals affected with hirschsprung disease (PMID: 9090527, 22174939). ClinVar contains an entry for this variant (Variation ID: 13932). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 27, 2021

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