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NM_020975.6(RET):c.2332G>A (p.Val778Ile) AND Multiple endocrine neoplasia, type 2

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 20, 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:
RCV000206045.16

Allele description [Variation Report for NM_020975.6(RET):c.2332G>A (p.Val778Ile)]

NM_020975.6(RET):c.2332G>A (p.Val778Ile)

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.2332G>A (p.Val778Ile)
HGVS:
  • NC_000010.11:g.43118420G>A
  • NG_007489.1:g.46352G>A
  • NM_000323.2:c.2332G>A
  • NM_001355216.2:c.1570G>A
  • NM_001406743.1:c.2332G>A
  • NM_001406744.1:c.2332G>A
  • NM_001406759.1:c.2332G>A
  • NM_001406760.1:c.2332G>A
  • NM_001406761.1:c.2203G>A
  • NM_001406762.1:c.2203G>A
  • NM_001406763.1:c.2197G>A
  • NM_001406764.1:c.2203G>A
  • NM_001406765.1:c.2197G>A
  • NM_001406766.1:c.2044G>A
  • NM_001406767.1:c.2044G>A
  • NM_001406768.1:c.2068G>A
  • NM_001406769.1:c.1936G>A
  • NM_001406770.1:c.2044G>A
  • NM_001406771.1:c.1894G>A
  • NM_001406772.1:c.1936G>A
  • NM_001406773.1:c.1894G>A
  • NM_001406774.1:c.1807G>A
  • NM_001406775.1:c.1606G>A
  • NM_001406776.1:c.1606G>A
  • NM_001406777.1:c.1606G>A
  • NM_001406778.1:c.1606G>A
  • NM_001406779.1:c.1435G>A
  • NM_001406780.1:c.1435G>A
  • NM_001406781.1:c.1435G>A
  • NM_001406782.1:c.1435G>A
  • NM_001406783.1:c.1306G>A
  • NM_001406784.1:c.1342G>A
  • NM_001406785.1:c.1315G>A
  • NM_001406786.1:c.1306G>A
  • NM_001406787.1:c.1300G>A
  • NM_001406788.1:c.1147G>A
  • NM_001406789.1:c.1147G>A
  • NM_001406790.1:c.1147G>A
  • NM_001406791.1:c.1027G>A
  • NM_001406792.1:c.883G>A
  • NM_001406793.1:c.883G>A
  • NM_001406794.1:c.883G>A
  • NM_020629.2:c.2332G>A
  • NM_020630.7:c.2332G>A
  • NM_020975.6:c.2332G>AMANE SELECT
  • NP_000314.1:p.Val778Ile
  • NP_001342145.1:p.Val524Ile
  • NP_001342145.1:p.Val524Ile
  • NP_001393672.1:p.Val778Ile
  • NP_001393673.1:p.Val778Ile
  • NP_001393688.1:p.Val778Ile
  • NP_001393689.1:p.Val778Ile
  • NP_001393690.1:p.Val735Ile
  • NP_001393691.1:p.Val735Ile
  • NP_001393692.1:p.Val733Ile
  • NP_001393693.1:p.Val735Ile
  • NP_001393694.1:p.Val733Ile
  • NP_001393695.1:p.Val682Ile
  • NP_001393696.1:p.Val682Ile
  • NP_001393697.1:p.Val690Ile
  • NP_001393698.1:p.Val646Ile
  • NP_001393699.1:p.Val682Ile
  • NP_001393700.1:p.Val632Ile
  • NP_001393701.1:p.Val646Ile
  • NP_001393702.1:p.Val632Ile
  • NP_001393703.1:p.Val603Ile
  • NP_001393704.1:p.Val536Ile
  • NP_001393705.1:p.Val536Ile
  • NP_001393706.1:p.Val536Ile
  • NP_001393707.1:p.Val536Ile
  • NP_001393708.1:p.Val479Ile
  • NP_001393709.1:p.Val479Ile
  • NP_001393710.1:p.Val479Ile
  • NP_001393711.1:p.Val479Ile
  • NP_001393712.1:p.Val436Ile
  • NP_001393713.1:p.Val448Ile
  • NP_001393714.1:p.Val439Ile
  • NP_001393715.1:p.Val436Ile
  • NP_001393716.1:p.Val434Ile
  • NP_001393717.1:p.Val383Ile
  • NP_001393718.1:p.Val383Ile
  • NP_001393719.1:p.Val383Ile
  • NP_001393720.1:p.Val343Ile
  • NP_001393721.1:p.Val295Ile
  • NP_001393722.1:p.Val295Ile
  • NP_001393723.1:p.Val295Ile
  • NP_065680.1:p.Val778Ile
  • NP_065681.1:p.Val778Ile
  • NP_065681.1:p.Val778Ile
  • NP_065681.1:p.Val778Ile
  • NP_066124.1:p.Val778Ile
  • NP_066124.1:p.Val778Ile
  • LRG_518t1:c.2332G>A
  • LRG_518t2:c.2332G>A
  • LRG_518:g.46352G>A
  • LRG_518p1:p.Val778Ile
  • LRG_518p2:p.Val778Ile
  • NC_000010.10:g.43613868G>A
  • NM_001355216.1:c.1570G>A
  • NM_020630.4:c.2332G>A
  • NM_020630.6:c.2332G>A
  • NM_020975.4:c.2332G>A
  • P07949:p.Val778Ile
Protein change:
V295I; VAL778ILE
Links:
UniProtKB: P07949#VAR_044395; OMIM: 164761.0053; dbSNP: rs75686697
NCBI 1000 Genomes Browser:
rs75686697
Molecular consequence:
  • NM_000323.2:c.2332G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001355216.2:c.1570G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406743.1:c.2332G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406744.1:c.2332G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406759.1:c.2332G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406760.1:c.2332G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406761.1:c.2203G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406762.1:c.2203G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406763.1:c.2197G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406764.1:c.2203G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406765.1:c.2197G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406766.1:c.2044G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406767.1:c.2044G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406768.1:c.2068G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406769.1:c.1936G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406770.1:c.2044G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406771.1:c.1894G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406772.1:c.1936G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406773.1:c.1894G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406774.1:c.1807G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406775.1:c.1606G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406776.1:c.1606G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406777.1:c.1606G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406778.1:c.1606G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406779.1:c.1435G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406780.1:c.1435G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406781.1:c.1435G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406782.1:c.1435G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406783.1:c.1306G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406784.1:c.1342G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406785.1:c.1315G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406786.1:c.1306G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406787.1:c.1300G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406788.1:c.1147G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406789.1:c.1147G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406790.1:c.1147G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406791.1:c.1027G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406792.1:c.883G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406793.1:c.883G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406794.1:c.883G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020629.2:c.2332G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020630.7:c.2332G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020975.6:c.2332G>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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000259848Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 20, 2022) 		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

Familial medullary thyroid carcinoma and prominent corneal nerves associated with the germline V804M and V778I mutations on the same allele of RET.

Kasprzak L, Nolet S, Gaboury L, Pavia C, Villabona C, Rivera-Fillat F, Oriola J, Foulkes WD.

J Med Genet. 2001 Nov;38(11):784-7. No abstract available.

PubMed [citation]
PMID:
11732489
PMCID:
PMC1734769

Prospective trial of unilateral surgery for nonhereditary medullary thyroid carcinoma in patients without germline RET mutations.

Miyauchi A, Matsuzuka F, Hirai K, Yokozawa T, Kobayashi K, Ito Y, Nakano K, Kuma K, Futami H, Yamaguchi K.

World J Surg. 2002 Aug;26(8):1023-8. Epub 2002 May 21.

PubMed [citation]
PMID:
12016484
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000259848.8

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

Description

This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 778 of the RET protein (p.Val778Ile). This variant is present in population databases (rs75686697, gnomAD 0.006%). This missense change has been observed in individual(s) with familial medullary thyroid cancer and bilateral renal aplasia (PMID: 11732489, 12016484, 18252215, 30927507). ClinVar contains an entry for this variant (Variation ID: 13955). An algorithm developed specifically for the RET gene suggests that this missense change is likely to be tolerated (PMID: 21479187). Experimental studies have shown that this missense change affects RET function (PMID: 18252215). 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 26, 2024