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NM_020975.6(RET):c.3182T>C (p.Leu1061Pro) AND Multiple endocrine neoplasia, type 2

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 13, 2022
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:
RCV000198421.4

Allele description [Variation Report for NM_020975.6(RET):c.3182T>C (p.Leu1061Pro)]

NM_020975.6(RET):c.3182T>C (p.Leu1061Pro)

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.3182T>C (p.Leu1061Pro)
HGVS:
  • NC_000010.11:g.43126717T>C
  • NG_007489.1:g.54649T>C
  • NM_000323.2:c.3182T>C
  • NM_001355216.2:c.2420T>C
  • NM_001406743.1:c.3182T>C
  • NM_001406744.1:c.3182T>C
  • NM_001406761.1:c.3053T>C
  • NM_001406762.1:c.3053T>C
  • NM_001406763.1:c.3047T>C
  • NM_001406764.1:c.3053T>C
  • NM_001406765.1:c.3047T>C
  • NM_001406766.1:c.2894T>C
  • NM_001406767.1:c.2894T>C
  • NM_001406768.1:c.2918T>C
  • NM_001406769.1:c.2786T>C
  • NM_001406770.1:c.2894T>C
  • NM_001406771.1:c.2744T>C
  • NM_001406772.1:c.2786T>C
  • NM_001406773.1:c.2744T>C
  • NM_001406774.1:c.2657T>C
  • NM_001406775.1:c.2456T>C
  • NM_001406776.1:c.2456T>C
  • NM_001406778.1:c.2456T>C
  • NM_001406779.1:c.2285T>C
  • NM_001406780.1:c.2285T>C
  • NM_001406781.1:c.2285T>C
  • NM_001406782.1:c.2285T>C
  • NM_001406783.1:c.2156T>C
  • NM_001406784.1:c.2192T>C
  • NM_001406785.1:c.2165T>C
  • NM_001406786.1:c.2156T>C
  • NM_001406787.1:c.2150T>C
  • NM_001406788.1:c.1997T>C
  • NM_001406789.1:c.1997T>C
  • NM_001406790.1:c.1997T>C
  • NM_001406791.1:c.1877T>C
  • NM_001406792.1:c.1733T>C
  • NM_001406794.1:c.1733T>C
  • NM_020629.2:c.3182T>C
  • NM_020630.7:c.3182T>C
  • NM_020975.6:c.3182T>CMANE SELECT
  • NP_000314.1:p.Leu1061Pro
  • NP_001342145.1:p.Leu807Pro
  • NP_001342145.1:p.Leu807Pro
  • NP_001393672.1:p.Leu1061Pro
  • NP_001393673.1:p.Leu1061Pro
  • NP_001393690.1:p.Leu1018Pro
  • NP_001393691.1:p.Leu1018Pro
  • NP_001393692.1:p.Leu1016Pro
  • NP_001393693.1:p.Leu1018Pro
  • NP_001393694.1:p.Leu1016Pro
  • NP_001393695.1:p.Leu965Pro
  • NP_001393696.1:p.Leu965Pro
  • NP_001393697.1:p.Leu973Pro
  • NP_001393698.1:p.Leu929Pro
  • NP_001393699.1:p.Leu965Pro
  • NP_001393700.1:p.Leu915Pro
  • NP_001393701.1:p.Leu929Pro
  • NP_001393702.1:p.Leu915Pro
  • NP_001393703.1:p.Leu886Pro
  • NP_001393704.1:p.Leu819Pro
  • NP_001393705.1:p.Leu819Pro
  • NP_001393707.1:p.Leu819Pro
  • NP_001393708.1:p.Leu762Pro
  • NP_001393709.1:p.Leu762Pro
  • NP_001393710.1:p.Leu762Pro
  • NP_001393711.1:p.Leu762Pro
  • NP_001393712.1:p.Leu719Pro
  • NP_001393713.1:p.Leu731Pro
  • NP_001393714.1:p.Leu722Pro
  • NP_001393715.1:p.Leu719Pro
  • NP_001393716.1:p.Leu717Pro
  • NP_001393717.1:p.Leu666Pro
  • NP_001393718.1:p.Leu666Pro
  • NP_001393719.1:p.Leu666Pro
  • NP_001393720.1:p.Leu626Pro
  • NP_001393721.1:p.Leu578Pro
  • NP_001393723.1:p.Leu578Pro
  • NP_065680.1:p.Leu1061Pro
  • NP_065681.1:p.Leu1061Pro
  • NP_065681.1:p.Leu1061Pro
  • NP_065681.1:p.Leu1061Pro
  • NP_066124.1:p.Leu1061Pro
  • NP_066124.1:p.Leu1061Pro
  • LRG_518t1:c.3182T>C
  • LRG_518t2:c.3182T>C
  • LRG_518:g.54649T>C
  • LRG_518p1:p.Leu1061Pro
  • LRG_518p2:p.Leu1061Pro
  • NC_000010.10:g.43622165T>C
  • NM_001355216.1:c.2420T>C
  • NM_020630.4:c.3182T>C
  • NM_020630.6:c.3182T>C
  • NM_020975.4:c.3182T>C
  • P07949:p.Leu1061Pro
Protein change:
L1016P
Links:
UniProtKB: P07949#VAR_009490; dbSNP: rs536486113
NCBI 1000 Genomes Browser:
rs536486113
Molecular consequence:
  • NM_000323.2:c.3182T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001355216.2:c.2420T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406743.1:c.3182T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406744.1:c.3182T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406761.1:c.3053T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406762.1:c.3053T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406763.1:c.3047T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406764.1:c.3053T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406765.1:c.3047T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406766.1:c.2894T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406767.1:c.2894T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406768.1:c.2918T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406769.1:c.2786T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406770.1:c.2894T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406771.1:c.2744T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406772.1:c.2786T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406773.1:c.2744T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406774.1:c.2657T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406775.1:c.2456T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406776.1:c.2456T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406778.1:c.2456T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406779.1:c.2285T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406780.1:c.2285T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406781.1:c.2285T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406782.1:c.2285T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406783.1:c.2156T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406784.1:c.2192T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406785.1:c.2165T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406786.1:c.2156T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406787.1:c.2150T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406788.1:c.1997T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406789.1:c.1997T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406790.1:c.1997T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406791.1:c.1877T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406792.1:c.1733T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406794.1:c.1733T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020629.2:c.3182T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020630.7:c.3182T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020975.6:c.3182T>C - 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000255054Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jun 13, 2022) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

The role of amino acids surrounding tyrosine 1062 in ret in specific binding of the shc phosphotyrosine-binding domain.

Ishiguro Y, Iwashita T, Murakami H, Asai N, Iida K, Goto H, Hayakawa T, Takahashi M.

Endocrinology. 1999 Sep;140(9):3992-8.

PubMed [citation]
PMID:
10465268

Two distinct mutations of the RET receptor causing Hirschsprung's disease impair the binding of signalling effectors to a multifunctional docking site.

Geneste O, Bidaud C, De Vita G, Hofstra RM, Tartare-Deckert S, Buys CH, Lenoir GM, Santoro M, Billaud M.

Hum Mol Genet. 1999 Oct;8(11):1989-99.

PubMed [citation]
PMID:
10484767
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000255054.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1061 of the RET protein (p.Leu1061Pro). This variant is present in population databases (rs536486113, gnomAD 0.003%). This missense change has been observed in individual(s) with Hirschsprung disease (PMID: 10484767). ClinVar contains an entry for this variant (Variation ID: 216725). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects RET function (PMID: 10465268, 10484767, 11313948, 11390647). 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: Apr 20, 2024