NM_020975.4(RET):c.2372A>T (p.Tyr791Phe) AND Pheochromocytoma

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Pathogenic(1) (Last evaluated: Jun 14, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000014963.28

Allele description

NM_020975.4(RET):c.2372A>T (p.Tyr791Phe)

Gene:
RET:ret proto-oncogene [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q11.21
Genomic location:
Preferred name:
NM_020975.4(RET):c.2372A>T (p.Tyr791Phe)
Other names:
p.Y791F:TAT>TTT
HGVS:
  • NC_000010.11:g.43118460A>T
  • NG_007489.1:g.46392A>T
  • NM_020630.4:c.2372A>T
  • NM_020975.4:c.2372A>T
  • NP_065681.1:p.Tyr791Phe
  • NP_066124.1:p.Tyr791Phe
  • LRG_518t1:c.2372A>T
  • LRG_518t2:c.2372A>T
  • LRG_518:g.46392A>T
  • LRG_518p1:p.Tyr791Phe
  • LRG_518p2:p.Tyr791Phe
  • NC_000010.10:g.43613908A>T
  • P07949:p.Tyr791Phe
Protein change:
Y791F; TYR791PHE
Links:
UniProtKB: P07949#VAR_009483; OMIM: 164761.0034; dbSNP: rs77724903
GMAF:
0.0002(T), 77724903
NCBI 1000 Genomes Browser:
rs77724903
Allele Frequency:
0.0012, GO-ESP
Molecular consequence:
  • NM_020975.4:c.2372A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Pheochromocytoma
Synonyms:
TMEM127-Related Pheochromocytoma; Pheochromocytoma, somatic; MAX-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome; See all synonyms [MedGen]
Identifiers:
MedGen: C0031511; Orphanet: 29072; OMIM: 171300; Human Phenotype Ontology: HP:0002666

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000035219OMIMno assertion criteria providedPathogenic
(Nov 1, 2005)
germlineliterature only

PubMed (4)
[See all records that cite these PMIDs]

SCV000362348Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Likely benign
(Jun 14, 2016)
germlineclinical testing

ICSL_Variant_Classification_20161018.pdf

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A new hot spot for mutations in the ret protooncogene causing familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2A.

Berndt I, Reuter M, Saller B, Frank-Raue K, Groth P, Grussendorf M, Raue F, Ritter MM, Höppner W.

J Clin Endocrinol Metab. 1998 Mar;83(3):770-4.

PubMed [citation]
PMID:
9506724

Germ-line mutations in nonsyndromic pheochromocytoma.

Neumann HP, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Smith WM, Munk R, Manz T, Glaesker S, Apel TW, Treier M, Reineke M, Walz MK, Hoang-Vu C, Brauckhoff M, et al.

N Engl J Med. 2002 May 9;346(19):1459-66.

PubMed [citation]
PMID:
12000816
See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000035219.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (4)

Description

See (164761.0033) and Berndt et al. (1998).

In a patient with sporadic pheochromocytoma (171300), Neumann et al. (2002) identified the tyr791-to-phe (Y791F) substitution resulting from a 2372A-T transversion in exon 13 of the RET gene. The mutation was not identified in 600 control chromosomes.

Baumgartner-Parzer et al. (2005) found that in patients with familial medullary thyroid carcinoma, the Y791F mutation (which the authors referred to as PHE791TYR, F791Y) was associated with the nearby L769L SNP. All 12 individuals carrying Y791F (9 unrelated individuals and 3 descendants) were homozygous or heterozygous for the L769L polymorphism.

Frank-Raue et al. (2005) found this mutation coincident with a splice site mutation in MEN1 (131100.0034) in 3 members of a family with a multiple endocrine neoplasia phenotype. The RET Y791F mutation was carried in isolation by the father, who at 65 years of age had no thyroid or parathyroid disease and no pheochromocytoma, and no family history of medullary thyroid carcinoma, pheochromocytoma, or primary hyperparathyroidism. The authors concluded that the RET Y791F mutation and the MEN1 mutation did not interact.

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

From Illumina Clinical Services Laboratory,Illumina, SCV000362348.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 2, 2018