NM_020975.6(RET):c.1424G>A (p.Arg475Gln) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 18, 2024
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:: RCV001011481.5

Allele description [Variation Report for NM_020975.6(RET):c.1424G>A (p.Arg475Gln)]

NM_020975.6(RET):c.1424G>A (p.Arg475Gln)

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.1424G>A (p.Arg475Gln)

HGVS:

NC_000010.11:g.43111367G>A
NG_007489.1:g.39299G>A
NM_000323.2:c.1424G>A
NM_001355216.2:c.662G>A
NM_001406743.1:c.1424G>A
NM_001406744.1:c.1424G>A
NM_001406759.1:c.1424G>A
NM_001406760.1:c.1424G>A
NM_001406761.1:c.1295G>A
NM_001406762.1:c.1295G>A
NM_001406763.1:c.1424G>A
NM_001406764.1:c.1295G>A
NM_001406765.1:c.1424G>A
NM_001406766.1:c.1136G>A
NM_001406767.1:c.1136G>A
NM_001406768.1:c.1295G>A
NM_001406769.1:c.1028G>A
NM_001406770.1:c.1136G>A
NM_001406771.1:c.986G>A
NM_001406772.1:c.1028G>A
NM_001406773.1:c.986G>A
NM_001406774.1:c.899G>A
NM_001406775.1:c.698G>A
NM_001406776.1:c.698G>A
NM_001406777.1:c.698G>A
NM_001406778.1:c.698G>A
NM_001406784.1:c.434G>A
NM_020629.2:c.1424G>A
NM_020630.7:c.1424G>A
NM_020975.6:c.1424G>AMANE SELECT
NP_000314.1:p.Arg475Gln
NP_001342145.1:p.Arg221Gln
NP_001342145.1:p.Arg221Gln
NP_001393672.1:p.Arg475Gln
NP_001393673.1:p.Arg475Gln
NP_001393688.1:p.Arg475Gln
NP_001393689.1:p.Arg475Gln
NP_001393690.1:p.Arg432Gln
NP_001393691.1:p.Arg432Gln
NP_001393692.1:p.Arg475Gln
NP_001393693.1:p.Arg432Gln
NP_001393694.1:p.Arg475Gln
NP_001393695.1:p.Arg379Gln
NP_001393696.1:p.Arg379Gln
NP_001393697.1:p.Arg432Gln
NP_001393698.1:p.Arg343Gln
NP_001393699.1:p.Arg379Gln
NP_001393700.1:p.Arg329Gln
NP_001393701.1:p.Arg343Gln
NP_001393702.1:p.Arg329Gln
NP_001393703.1:p.Arg300Gln
NP_001393704.1:p.Arg233Gln
NP_001393705.1:p.Arg233Gln
NP_001393706.1:p.Arg233Gln
NP_001393707.1:p.Arg233Gln
NP_001393713.1:p.Arg145Gln
NP_065680.1:p.Arg475Gln
NP_065681.1:p.Arg475Gln
NP_065681.1:p.Arg475Gln
NP_065681.1:p.Arg475Gln
NP_066124.1:p.Arg475Gln
NP_066124.1:p.Arg475Gln
LRG_518t1:c.1424G>A
LRG_518t2:c.1424G>A
LRG_518:g.39299G>A
LRG_518p1:p.Arg475Gln
LRG_518p2:p.Arg475Gln
NC_000010.10:g.43606815G>A
NM_001355216.1:c.662G>A
NM_020630.4:c.1424G>A
NM_020630.6:c.1424G>A
NM_020975.4:c.1424G>A
P07949:p.Arg475Gln

Protein change:

R145Q

Links:

UniProtKB: P07949#VAR_006305; dbSNP: rs138624658

NCBI 1000 Genomes Browser:

rs138624658

Molecular consequence:

NM_000323.2:c.1424G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001355216.2:c.662G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406743.1:c.1424G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406744.1:c.1424G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406759.1:c.1424G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406760.1:c.1424G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406761.1:c.1295G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406762.1:c.1295G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406763.1:c.1424G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406764.1:c.1295G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406765.1:c.1424G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406766.1:c.1136G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406767.1:c.1136G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406768.1:c.1295G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406769.1:c.1028G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406770.1:c.1136G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406771.1:c.986G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406772.1:c.1028G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406773.1:c.986G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406774.1:c.899G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406775.1:c.698G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406776.1:c.698G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406777.1:c.698G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406778.1:c.698G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406784.1:c.434G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020629.2:c.1424G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020630.7:c.1424G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020975.6:c.1424G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Hereditary neoplastic syndrome; 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
SCV001171807	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Apr 18, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24728327, 25637381, 30122538, 7581377 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001171807

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Apr 18, 2024)

germline

clinical testing

PubMed (4)
[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

Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

Bodian DL, McCutcheon JN, Kothiyal P, Huddleston KC, Iyer RK, Vockley JG, Niederhuber JE.

PLoS One. 2014;9(4):e94554. doi: 10.1371/journal.pone.0094554.

PubMed [citation]

PMID:: 24728327
PMCID:: PMC3984285

Actionable exomic incidental findings in 6503 participants: challenges of variant classification.

Amendola LM, Dorschner MO, Robertson PD, Salama JS, Hart R, Shirts BH, Murray ML, Tokita MJ, Gallego CJ, Kim DS, Bennett JT, Crosslin DR, Ranchalis J, Jones KL, Rosenthal EA, Jarvik ER, Itsara A, Turner EH, Herman DS, Schleit J, Burt A, Jamal SM, et al.

Genome Res. 2015 Mar;25(3):305-15. doi: 10.1101/gr.183483.114. Epub 2015 Jan 30.

PubMed [citation]

PMID:: 25637381
PMCID:: PMC4352885

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV001171807.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The p.R475Q variant (also known as c.1424G>A), located in coding exon 7 of the RET gene, results from a G to A substitution at nucleotide position 1424. The arginine at codon 475 is replaced by glutamine, an amino acid with highly similar properties. This variant has been reported in a patient with sporadic Hirschsprung disease (Attié T et al. Hum. Mol. Genet. 1995 Aug;4:1381-6). This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: May 16, 2025

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