NM_001048174.2(MUTYH):c.466C>T (p.Arg156Trp) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Oct 10, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000485428.5

Allele description [Variation Report for NM_001048174.2(MUTYH):c.466C>T (p.Arg156Trp)]

NM_001048174.2(MUTYH):c.466C>T (p.Arg156Trp)

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.466C>T (p.Arg156Trp)
HGVS:
  • NC_000001.11:g.45332789G>A
  • NG_008189.1:g.12682C>T
  • NM_001048171.1:c.508C>T
  • NM_001048171.2:c.466C>T
  • NM_001048172.1:c.469C>T
  • NM_001048173.1:c.466C>T
  • NM_001048174.2:c.466C>TMANE SELECT
  • NM_001128425.1:c.550C>T
  • NM_001128425.2:c.550C>T
  • NM_001293190.1:c.511C>T
  • NM_001293191.1:c.499C>T
  • NM_001293192.1:c.190C>T
  • NM_001293195.1:c.466C>T
  • NM_001293196.1:c.190C>T
  • NM_001350650.1:c.121C>T
  • NM_001350651.1:c.121C>T
  • NM_012222.2:c.541C>T
  • NP_001041636.1:p.Arg170Trp
  • NP_001041636.2:p.Arg156Trp
  • NP_001041637.1:p.Arg157Trp
  • NP_001041638.1:p.Arg156Trp
  • NP_001041639.1:p.Arg156Trp
  • NP_001121897.1:p.Arg184Trp
  • NP_001121897.1:p.Arg184Trp
  • NP_001280119.1:p.Arg171Trp
  • NP_001280120.1:p.Arg167Trp
  • NP_001280121.1:p.Arg64Trp
  • NP_001280124.1:p.Arg156Trp
  • NP_001280125.1:p.Arg64Trp
  • NP_001337579.1:p.Arg41Trp
  • NP_001337580.1:p.Arg41Trp
  • NP_036354.1:p.Arg181Trp
  • LRG_220t1:c.550C>T
  • LRG_220:g.12682C>T
  • LRG_220p1:p.Arg184Trp
  • NC_000001.10:g.45798461G>A
  • NR_146882.1:n.724C>T
  • NR_146883.1:n.538C>T
  • p.R184W
Protein change:
R156W
Links:
dbSNP: rs779997419
NCBI 1000 Genomes Browser:
rs779997419
Molecular consequence:
  • NM_001048171.1:c.508C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048171.2:c.466C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.1:c.469C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.1:c.466C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.2:c.466C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.1:c.550C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.2:c.550C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.1:c.511C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.1:c.499C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293192.1:c.190C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.1:c.466C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293196.1:c.190C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350650.1:c.121C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350651.1:c.121C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.2:c.541C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.1:n.724C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.1:n.538C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000601652Quest Diagnostics Nichols Institute San Juan Capistranocriteria provided, single submitter
Uncertain significance
(Nov 22, 2016)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV000713011Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Mar 6, 2017)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001361133Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Oct 10, 2019)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020
See all PubMed Citations (4)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000601652.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000713011.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The p.Arg184Trp variant in MUTYH has been reported, along with a second MUTYH va riant of uncertain significance (phase unknown), in one Spanish individual with multiple adenomas and colorectal cancer (Gomez-Fernandez 2009) and has also been reported in ClinVar (Variation ID# 187318). In addition, this variant has been identified in 1/66738 of European chromosomes by the Exome Aggregation Consortiu m (ExAC, http://exac.broadinstitute.org; dbSNP rs779997419). Although the p.Arg1 84Trp variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conser vation analysis do not provide strong support for or against an impact to the pr otein. In summary, the clinical significance of the p.Arg184Trp variant is uncer tain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361133.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: MUTYH c.550C>T (p.Arg184Trp) results in a non-conservative amino acid change located in the HhH-GPD domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251460 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.550C>T has been reported in the literature in individual with multiple adenomas and colorectal cancer (Gomez-Fernandez_2009) and in an individual suspected of MAP (Ricci_2016), both without strong evidence of causality. These reports do not provide unequivocal conclusions about association of the variant with MUTYH-associated Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Sep 26, 2021

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