NM_020975.6(RET):c.718G>C (p.Val240Leu) AND Hirschsprung disease, susceptibility to, 1

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 29, 2023
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:: RCV001103893.6

Allele description [Variation Report for NM_020975.6(RET):c.718G>C (p.Val240Leu)]

NM_020975.6(RET):c.718G>C (p.Val240Leu)

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.718G>C (p.Val240Leu)

HGVS:

NC_000010.11:g.43105044G>C
NG_007489.1:g.32976G>C
NM_000323.2:c.718G>C
NM_001355216.2:c.-45G>C
NM_001406743.1:c.718G>C
NM_001406744.1:c.718G>C
NM_001406759.1:c.718G>C
NM_001406760.1:c.718G>C
NM_001406761.1:c.589G>C
NM_001406762.1:c.589G>C
NM_001406763.1:c.718G>C
NM_001406764.1:c.589G>C
NM_001406765.1:c.718G>C
NM_001406766.1:c.430G>C
NM_001406767.1:c.430G>C
NM_001406768.1:c.589G>C
NM_001406769.1:c.718G>C
NM_001406770.1:c.430G>C
NM_001406772.1:c.718G>C
NM_001406774.1:c.589G>C
NM_020629.2:c.718G>C
NM_020630.7:c.718G>C
NM_020975.6:c.718G>CMANE SELECT
NP_000314.1:p.Val240Leu
NP_001393672.1:p.Val240Leu
NP_001393673.1:p.Val240Leu
NP_001393688.1:p.Val240Leu
NP_001393689.1:p.Val240Leu
NP_001393690.1:p.Val197Leu
NP_001393691.1:p.Val197Leu
NP_001393692.1:p.Val240Leu
NP_001393693.1:p.Val197Leu
NP_001393694.1:p.Val240Leu
NP_001393695.1:p.Val144Leu
NP_001393696.1:p.Val144Leu
NP_001393697.1:p.Val197Leu
NP_001393698.1:p.Val240Leu
NP_001393699.1:p.Val144Leu
NP_001393701.1:p.Val240Leu
NP_001393703.1:p.Val197Leu
NP_065680.1:p.Val240Leu
NP_065681.1:p.Val240Leu
NP_065681.1:p.Val240Leu
NP_065681.1:p.Val240Leu
NP_066124.1:p.Val240Leu
NP_066124.1:p.Val240Leu
LRG_518t1:c.718G>C
LRG_518t2:c.718G>C
LRG_518:g.32976G>C
LRG_518p1:p.Val240Leu
LRG_518p2:p.Val240Leu
NC_000010.10:g.43600492G>C
NM_001355216.1:c.-45G>C
NM_020630.4:c.718G>C
NM_020630.6:c.718G>C
NM_020975.4:c.718G>C

Protein change:

V144L

Links:

dbSNP: rs375120544

NCBI 1000 Genomes Browser:

rs375120544

Molecular consequence:

NM_000323.2:c.718G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406743.1:c.718G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406744.1:c.718G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406759.1:c.718G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406760.1:c.718G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406761.1:c.589G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406762.1:c.589G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406763.1:c.718G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406764.1:c.589G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406765.1:c.718G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406766.1:c.430G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406767.1:c.430G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406768.1:c.589G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406769.1:c.718G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406770.1:c.430G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406772.1:c.718G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406774.1:c.589G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_020629.2:c.718G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_020630.7:c.718G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_020975.6:c.718G>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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Styela clava isolate 36 cytochrome oxidase subunit I (COI) gene, partial cds; mi...
Styela clava isolate 36 cytochrome oxidase subunit I (COI) gene, partial cds; mitochondrial
gi|220063637|gb|FJ528636.1|

Nucleotide
Superfamily Links for Conserved Domains (Select 407508) (1)
Conserved Domains
RecName: Full=Uncharacterized protein FLJ76381
RecName: Full=Uncharacterized protein FLJ76381
gi|74751271|sp|Q8NFD4.1|YI018_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001260706	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV004208670	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 29, 2023)	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

SCV001260706

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Jan 13, 2018)

germline

clinical testing

Citation Link,

SCV004208670

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 29, 2023)

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, SCV001260706.1

#	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 in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#	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, SCV004208670.1

#	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: May 7, 2024

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