NM_020975.6(RET):c.2332G>A (p.Val778Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely benign (1 submission)
Last evaluated:: Feb 26, 2020
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:: RCV000562190.12

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:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000674786	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Feb 26, 2020)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 11732489, 12016484, 18252215, 21479187, 27798940, 30927507 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000674786

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Feb 26, 2020)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Ambry Genetics, SCV000674786.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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