NM_001048174.2(MUTYH):c.461G>A (p.Arg154His) AND not provided

Clinical significance:Pathogenic (Last evaluated: Jun 30, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000160752.5

Allele description [Variation Report for NM_001048174.2(MUTYH):c.461G>A (p.Arg154His)]

NM_001048174.2(MUTYH):c.461G>A (p.Arg154His)

Gene:
MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_001048174.2(MUTYH):c.461G>A (p.Arg154His)
Other names:
p.R182H:CGT>CAT
HGVS:
  • NC_000001.11:g.45332794C>T
  • NG_008189.1:g.12677G>A
  • NM_001048171.2:c.461G>A
  • NM_001048172.1:c.464G>A
  • NM_001048173.1:c.461G>A
  • NM_001048174.2:c.461G>AMANE SELECT
  • NM_001128425.1:c.545G>A
  • NM_001128425.2:c.545G>A
  • NM_001293190.1:c.506G>A
  • NM_001293191.1:c.494G>A
  • NM_001293192.1:c.185G>A
  • NM_001293195.1:c.461G>A
  • NM_001293196.1:c.185G>A
  • NM_001350650.1:c.116G>A
  • NM_001350651.1:c.116G>A
  • NM_012222.2:c.536G>A
  • NP_001041636.2:p.Arg154His
  • NP_001041637.1:p.Arg155His
  • NP_001041638.1:p.Arg154His
  • NP_001041639.1:p.Arg154His
  • NP_001121897.1:p.Arg182His
  • NP_001121897.1:p.Arg182His
  • NP_001280119.1:p.Arg169His
  • NP_001280120.1:p.Arg165His
  • NP_001280121.1:p.Arg62His
  • NP_001280124.1:p.Arg154His
  • NP_001280125.1:p.Arg62His
  • NP_001337579.1:p.Arg39His
  • NP_001337580.1:p.Arg39His
  • NP_036354.1:p.Arg179His
  • LRG_220t1:c.545G>A
  • LRG_220:g.12677G>A
  • LRG_220p1:p.Arg182His
  • NC_000001.10:g.45798466C>T
  • NR_146882.1:n.719G>A
  • NR_146883.1:n.533G>A
Protein change:
R154H
Links:
dbSNP: rs143353451
NCBI 1000 Genomes Browser:
rs143353451
Molecular consequence:
  • NM_001048171.2:c.461G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.1:c.464G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.1:c.461G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.2:c.461G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.1:c.545G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.2:c.545G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.1:c.506G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.1:c.494G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293192.1:c.185G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.1:c.461G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293196.1:c.185G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350650.1:c.116G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350651.1:c.116G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.2:c.536G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.1:n.719G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.1:n.533G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000211402GeneDxcriteria provided, single submitter
Pathogenic
(Dec 17, 2019)
germlineclinical testing

Citation Link,

SCV001470576Quest Diagnostics Nichols Institute San Juan Capistranocriteria provided, single submitter
Pathogenic
(Jun 30, 2020)
unknownclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Inherited DNA-Repair Defects in Colorectal Cancer.

AlDubayan SH, Giannakis M, Moore ND, Han GC, Reardon B, Hamada T, Mu XJ, Nishihara R, Qian Z, Liu L, Yurgelun MB, Syngal S, Garraway LA, Ogino S, Fuchs CS, Van Allen EM.

Am J Hum Genet. 2018 Mar 1;102(3):401-414. doi: 10.1016/j.ajhg.2018.01.018. Epub 2018 Feb 22.

PubMed [citation]
PMID:
29478780
PMCID:
PMC5985280

Germline MUTYH (MYH) mutations in Portuguese individuals with multiple colorectal adenomas.

Isidro G, Laranjeira F, Pires A, Leite J, Regateiro F, Castro e Sousa F, Soares J, Castro C, Giria J, Brito MJ, Medeira A, Teixeira R, Morna H, Gaspar I, Marinho C, Jorge R, Brehm A, Ramos JS, Boavida MG.

Hum Mutat. 2004 Oct;24(4):353-4.

PubMed [citation]
PMID:
15366000
See all PubMed Citations (11)

Details of each submission

From GeneDx, SCV000211402.12

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Published functional studies demonstrate a damaging effect: severely affected glycosylation and suppression of oxidative mutagenesis (Goto 2010, Shinmura 2012, Komine 2015); Observed in the compound heterozygous state with known pathogenic variants in multiple individuals with a phenotype consistent with MUTYH-associated polyposis (MAP) (Isidro 2004, Aretz 2006, Di Gregorio 2006, Nielsen 2009, Morak 2010); This variant is associated with the following publications: (PMID: 20848659, 25820570, 16207212, 17273161, 19032956, 23507534, 30604180, 23322991, 15366000, 14961129, 16890597, 16557584, 19394335, 20618354, 23605219, 21901162, 26681312, 28452373, 27783336, 29478780, 30291343, 32283892, 31589614)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001470576.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

The best available variant frequency is uninformative because it is below the disease allele frequency. Found in at least one patient with expected phenotype for this gene. Other pathogenic or likely pathogenic variants affect the same amino acid . In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. Assessment of experimental evidence suggests this variant results in abnormal protein function.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 26, 2021

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