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NM_020975.6(RET):c.2369T>C (p.Leu790Ser) AND Multiple endocrine neoplasia, type 2

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 7, 2023
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:
RCV003646532.1

Allele description [Variation Report for NM_020975.6(RET):c.2369T>C (p.Leu790Ser)]

NM_020975.6(RET):c.2369T>C (p.Leu790Ser)

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.2369T>C (p.Leu790Ser)
HGVS:
  • NC_000010.11:g.43118457T>C
  • NG_007489.1:g.46389T>C
  • NM_000323.2:c.2369T>C
  • NM_001355216.2:c.1607T>C
  • NM_001406743.1:c.2369T>C
  • NM_001406744.1:c.2369T>C
  • NM_001406759.1:c.2369T>C
  • NM_001406760.1:c.2369T>C
  • NM_001406761.1:c.2240T>C
  • NM_001406762.1:c.2240T>C
  • NM_001406763.1:c.2234T>C
  • NM_001406764.1:c.2240T>C
  • NM_001406765.1:c.2234T>C
  • NM_001406766.1:c.2081T>C
  • NM_001406767.1:c.2081T>C
  • NM_001406768.1:c.2105T>C
  • NM_001406769.1:c.1973T>C
  • NM_001406770.1:c.2081T>C
  • NM_001406771.1:c.1931T>C
  • NM_001406772.1:c.1973T>C
  • NM_001406773.1:c.1931T>C
  • NM_001406774.1:c.1844T>C
  • NM_001406775.1:c.1643T>C
  • NM_001406776.1:c.1643T>C
  • NM_001406777.1:c.1643T>C
  • NM_001406778.1:c.1643T>C
  • NM_001406779.1:c.1472T>C
  • NM_001406780.1:c.1472T>C
  • NM_001406781.1:c.1472T>C
  • NM_001406782.1:c.1472T>C
  • NM_001406783.1:c.1343T>C
  • NM_001406784.1:c.1379T>C
  • NM_001406785.1:c.1352T>C
  • NM_001406786.1:c.1343T>C
  • NM_001406787.1:c.1337T>C
  • NM_001406788.1:c.1184T>C
  • NM_001406789.1:c.1184T>C
  • NM_001406790.1:c.1184T>C
  • NM_001406791.1:c.1064T>C
  • NM_001406792.1:c.920T>C
  • NM_001406793.1:c.920T>C
  • NM_001406794.1:c.920T>C
  • NM_020629.2:c.2369T>C
  • NM_020630.7:c.2369T>C
  • NM_020975.6:c.2369T>CMANE SELECT
  • NP_000314.1:p.Leu790Ser
  • NP_001342145.1:p.Leu536Ser
  • NP_001393672.1:p.Leu790Ser
  • NP_001393673.1:p.Leu790Ser
  • NP_001393688.1:p.Leu790Ser
  • NP_001393689.1:p.Leu790Ser
  • NP_001393690.1:p.Leu747Ser
  • NP_001393691.1:p.Leu747Ser
  • NP_001393692.1:p.Leu745Ser
  • NP_001393693.1:p.Leu747Ser
  • NP_001393694.1:p.Leu745Ser
  • NP_001393695.1:p.Leu694Ser
  • NP_001393696.1:p.Leu694Ser
  • NP_001393697.1:p.Leu702Ser
  • NP_001393698.1:p.Leu658Ser
  • NP_001393699.1:p.Leu694Ser
  • NP_001393700.1:p.Leu644Ser
  • NP_001393701.1:p.Leu658Ser
  • NP_001393702.1:p.Leu644Ser
  • NP_001393703.1:p.Leu615Ser
  • NP_001393704.1:p.Leu548Ser
  • NP_001393705.1:p.Leu548Ser
  • NP_001393706.1:p.Leu548Ser
  • NP_001393707.1:p.Leu548Ser
  • NP_001393708.1:p.Leu491Ser
  • NP_001393709.1:p.Leu491Ser
  • NP_001393710.1:p.Leu491Ser
  • NP_001393711.1:p.Leu491Ser
  • NP_001393712.1:p.Leu448Ser
  • NP_001393713.1:p.Leu460Ser
  • NP_001393714.1:p.Leu451Ser
  • NP_001393715.1:p.Leu448Ser
  • NP_001393716.1:p.Leu446Ser
  • NP_001393717.1:p.Leu395Ser
  • NP_001393718.1:p.Leu395Ser
  • NP_001393719.1:p.Leu395Ser
  • NP_001393720.1:p.Leu355Ser
  • NP_001393721.1:p.Leu307Ser
  • NP_001393722.1:p.Leu307Ser
  • NP_001393723.1:p.Leu307Ser
  • NP_065680.1:p.Leu790Ser
  • NP_065681.1:p.Leu790Ser
  • NP_065681.1:p.Leu790Ser
  • NP_066124.1:p.Leu790Ser
  • NP_066124.1:p.Leu790Ser
  • LRG_518t1:c.2369T>C
  • LRG_518t2:c.2369T>C
  • LRG_518:g.46389T>C
  • LRG_518p1:p.Leu790Ser
  • LRG_518p2:p.Leu790Ser
  • NC_000010.10:g.43613905T>C
  • NM_020630.4:c.2369T>C
  • NM_020975.4:c.2369T>C
Protein change:
L307S
Molecular consequence:
  • NM_000323.2:c.2369T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001355216.2:c.1607T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406743.1:c.2369T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406744.1:c.2369T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406759.1:c.2369T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406760.1:c.2369T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406761.1:c.2240T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406762.1:c.2240T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406763.1:c.2234T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406764.1:c.2240T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406765.1:c.2234T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406766.1:c.2081T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406767.1:c.2081T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406768.1:c.2105T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406769.1:c.1973T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406770.1:c.2081T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406771.1:c.1931T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406772.1:c.1973T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406773.1:c.1931T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406774.1:c.1844T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406775.1:c.1643T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406776.1:c.1643T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406777.1:c.1643T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406778.1:c.1643T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406779.1:c.1472T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406780.1:c.1472T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406781.1:c.1472T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406782.1:c.1472T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406783.1:c.1343T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406784.1:c.1379T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406785.1:c.1352T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406786.1:c.1343T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406787.1:c.1337T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406788.1:c.1184T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406789.1:c.1184T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406790.1:c.1184T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406791.1:c.1064T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406792.1:c.920T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406793.1:c.920T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406794.1:c.920T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020629.2:c.2369T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020630.7:c.2369T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020975.6:c.2369T>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
SCV004505731Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Mar 7, 2023) 		germlineclinical testing

PubMed (6)
[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

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

Various penetrance of familial medullary thyroid carcinoma in patients with RET protooncogene codon 790/791 germline mutations.

Fitze G, Schierz M, Bredow J, Saeger HD, Roesner D, Schackert HK.

Ann Surg. 2002 Nov;236(5):570-5.

PubMed [citation]
PMID:
12409662
PMCID:
PMC1422614
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV004505731.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

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. This variant disrupts the p.Leu790 amino acid residue in RET. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9506724, 12409662, 12490841, 21688339, 21810974). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 790 of the RET protein (p.Leu790Ser).

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

Last Updated: Jun 2, 2024