NM_020975.6(RET):c.1601T>C (p.Leu534Pro) AND Hirschsprung disease, susceptibility to, 1

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 10, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001102554.7

Allele description [Variation Report for NM_020975.6(RET):c.1601T>C (p.Leu534Pro)]

NM_020975.6(RET):c.1601T>C (p.Leu534Pro)

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.1601T>C (p.Leu534Pro)

HGVS:

NC_000010.11:g.43112177T>C
NG_007489.1:g.40109T>C
NM_000323.2:c.1601T>C
NM_001355216.2:c.839T>C
NM_001406743.1:c.1601T>C
NM_001406744.1:c.1601T>C
NM_001406759.1:c.1601T>C
NM_001406760.1:c.1601T>C
NM_001406761.1:c.1472T>C
NM_001406762.1:c.1472T>C
NM_001406763.1:c.1601T>C
NM_001406764.1:c.1472T>C
NM_001406765.1:c.1601T>C
NM_001406766.1:c.1313T>C
NM_001406767.1:c.1313T>C
NM_001406768.1:c.1472T>C
NM_001406769.1:c.1205T>C
NM_001406770.1:c.1313T>C
NM_001406771.1:c.1163T>C
NM_001406772.1:c.1205T>C
NM_001406773.1:c.1163T>C
NM_001406774.1:c.1076T>C
NM_001406775.1:c.875T>C
NM_001406776.1:c.875T>C
NM_001406777.1:c.875T>C
NM_001406778.1:c.875T>C
NM_001406779.1:c.704T>C
NM_001406780.1:c.704T>C
NM_001406781.1:c.704T>C
NM_001406782.1:c.704T>C
NM_001406783.1:c.575T>C
NM_001406784.1:c.611T>C
NM_001406785.1:c.704T>C
NM_001406786.1:c.575T>C
NM_001406787.1:c.704T>C
NM_001406788.1:c.416T>C
NM_001406789.1:c.416T>C
NM_001406790.1:c.416T>C
NM_001406791.1:c.416T>C
NM_001406792.1:c.152T>C
NM_001406793.1:c.152T>C
NM_001406794.1:c.152T>C
NM_020629.2:c.1601T>C
NM_020630.7:c.1601T>C
NM_020975.6:c.1601T>CMANE SELECT
NP_000314.1:p.Leu534Pro
NP_001342145.1:p.Leu280Pro
NP_001342145.1:p.Leu280Pro
NP_001393672.1:p.Leu534Pro
NP_001393673.1:p.Leu534Pro
NP_001393688.1:p.Leu534Pro
NP_001393689.1:p.Leu534Pro
NP_001393690.1:p.Leu491Pro
NP_001393691.1:p.Leu491Pro
NP_001393692.1:p.Leu534Pro
NP_001393693.1:p.Leu491Pro
NP_001393694.1:p.Leu534Pro
NP_001393695.1:p.Leu438Pro
NP_001393696.1:p.Leu438Pro
NP_001393697.1:p.Leu491Pro
NP_001393698.1:p.Leu402Pro
NP_001393699.1:p.Leu438Pro
NP_001393700.1:p.Leu388Pro
NP_001393701.1:p.Leu402Pro
NP_001393702.1:p.Leu388Pro
NP_001393703.1:p.Leu359Pro
NP_001393704.1:p.Leu292Pro
NP_001393705.1:p.Leu292Pro
NP_001393706.1:p.Leu292Pro
NP_001393707.1:p.Leu292Pro
NP_001393708.1:p.Leu235Pro
NP_001393709.1:p.Leu235Pro
NP_001393710.1:p.Leu235Pro
NP_001393711.1:p.Leu235Pro
NP_001393712.1:p.Leu192Pro
NP_001393713.1:p.Leu204Pro
NP_001393714.1:p.Leu235Pro
NP_001393715.1:p.Leu192Pro
NP_001393716.1:p.Leu235Pro
NP_001393717.1:p.Leu139Pro
NP_001393718.1:p.Leu139Pro
NP_001393719.1:p.Leu139Pro
NP_001393720.1:p.Leu139Pro
NP_001393721.1:p.Leu51Pro
NP_001393722.1:p.Leu51Pro
NP_001393723.1:p.Leu51Pro
NP_065680.1:p.Leu534Pro
NP_065681.1:p.Leu534Pro
NP_065681.1:p.Leu534Pro
NP_065681.1:p.Leu534Pro
NP_066124.1:p.Leu534Pro
NP_066124.1:p.Leu534Pro
LRG_518t1:c.1601T>C
LRG_518t2:c.1601T>C
LRG_518:g.40109T>C
LRG_518p1:p.Leu534Pro
LRG_518p2:p.Leu534Pro
NC_000010.10:g.43607625T>C
NC_000010.10:g.43607625T>C
NM_001355216.1:c.839T>C
NM_020630.4:c.1601T>C
NM_020630.6:c.1601T>C
NM_020975.4:c.1601T>C

Protein change:

L139P

Links:

dbSNP: rs1206429429

NCBI 1000 Genomes Browser:

rs1206429429

Molecular consequence:

NM_000323.2:c.1601T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001355216.2:c.839T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406743.1:c.1601T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406744.1:c.1601T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406759.1:c.1601T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406760.1:c.1601T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406761.1:c.1472T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406762.1:c.1472T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406763.1:c.1601T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406764.1:c.1472T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406765.1:c.1601T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406766.1:c.1313T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406767.1:c.1313T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406768.1:c.1472T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406769.1:c.1205T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406770.1:c.1313T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406771.1:c.1163T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406772.1:c.1205T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406773.1:c.1163T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406774.1:c.1076T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406775.1:c.875T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406776.1:c.875T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406777.1:c.875T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406778.1:c.875T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406779.1:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406780.1:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406781.1:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406782.1:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406783.1:c.575T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406784.1:c.611T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406785.1:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406786.1:c.575T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406787.1:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406788.1:c.416T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406789.1:c.416T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406790.1:c.416T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406791.1:c.416T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406792.1:c.152T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406793.1:c.152T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406794.1:c.152T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_020629.2:c.1601T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_020630.7:c.1601T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_020975.6:c.1601T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hirschsprung disease, susceptibility to, 1
Synonyms:: Hirschsprung disease 1; HSCR 1; RET-Related Hirschsprung Disease
Identifiers:: MONDO: MONDO:0007723; MedGen: C3888239; Orphanet: 388; OMIM: 142623

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001259235	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	Citation Link,
SCV005054193	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 10, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001259235

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

Citation Link,

SCV005054193

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 10, 2024)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001259235.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	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

From Baylor Genetics, SCV005054193.1

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

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

Last Updated: Sep 29, 2024

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