NM_001048171.1(MUTYH):c.1259C>T (p.Thr420Met) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Aug 13, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_001048171.1(MUTYH):c.1259C>T (p.Thr420Met)]

NM_001048171.1(MUTYH):c.1259C>T (p.Thr420Met)

MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001048171.1(MUTYH):c.1259C>T (p.Thr420Met)
Other names:
  • NC_000001.11:g.45331442G>A
  • NG_008189.1:g.14029C>T
  • NM_001048171.1:c.1259C>T
  • NM_001048172.1:c.1220C>T
  • NM_001048173.1:c.1217C>T
  • NM_001048174.1:c.1217C>T
  • NM_001128425.1:c.1301C>T
  • NM_001293190.1:c.1262C>T
  • NM_001293191.1:c.1250C>T
  • NM_001293192.1:c.941C>T
  • NM_001293195.1:c.1217C>T
  • NM_001293196.1:c.941C>T
  • NM_001350650.1:c.872C>T
  • NM_001350651.1:c.872C>T
  • NM_012222.2:c.1292C>T
  • NP_001041636.1:p.Thr420Met
  • NP_001041637.1:p.Thr407Met
  • NP_001041638.1:p.Thr406Met
  • NP_001041639.1:p.Thr406Met
  • NP_001121897.1:p.Thr434Met
  • NP_001280119.1:p.Thr421Met
  • NP_001280120.1:p.Thr417Met
  • NP_001280121.1:p.Thr314Met
  • NP_001280124.1:p.Thr406Met
  • NP_001280125.1:p.Thr314Met
  • NP_001337579.1:p.Thr291Met
  • NP_001337580.1:p.Thr291Met
  • NP_036354.1:p.Thr431Met
  • LRG_220t1:c.1301C>T
  • LRG_220:g.14029C>T
  • LRG_220p1:p.Thr434Met
  • NC_000001.10:g.45797114G>A
  • NR_146882.1:n.1475C>T
  • NR_146883.1:n.1289C>T
  • p.T434M
Protein change:
dbSNP: rs587780084
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001048171.1:c.1259C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.1:c.1220C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.1:c.1217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.1:c.1217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.1:c.1301C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.1:c.1262C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.1:c.1250C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293192.1:c.941C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.1:c.1217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293196.1:c.941C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350650.1:c.872C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350651.1:c.872C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.2:c.1292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.1:n.1475C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.1:n.1289C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000149666GeneDxcriteria provided, single submitter
Uncertain significance
(Jun 28, 2018)
germlineclinical testing

Citation Link,

SCV000888306Quest Diagnostics Nichols Institute San Juan Capistranocriteria provided, single submitter
Uncertain significance
(Aug 13, 2018)
germlineclinical testing

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

Summary from all submissions

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



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]

Details of each submission

From GeneDx, SCV000149666.14

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


This variant is denoted MUTYH c.1301C>T at the cDNA level, p.Thr434Met (T434M) at the protein level, and results in the change of a Threonine to a Methionine (ACG>ATG). This variant was identified in an individual with a personal history of a Lynch syndrome-associated cancer and/or polyps who underwent genetic testing for Lynch syndrome using a multi-gene panel (Yurgelun 2015). MUTYH Thr434Met was observed at an allele frequency of 0.009% (2/24,026) in individuals of African ancestry in large population cohorts (Lek 2016). This variant is located in the NUDIX domain (Ruggieri 2013). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether MUTYH Thr434Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. Of note, MUTYH-Associated Polyposis (MAP) is a recessive condition associated with two MUTYH pathogenic variants on opposite chromosomes.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000888306.1

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

Last Updated: Sep 29, 2021

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