NM_001048174.2(MUTYH):c.206G>A (p.Arg69Gln) AND Hereditary cancer-predisposing syndrome

Clinical significance:Uncertain significance (Last evaluated: Feb 21, 2020)

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_001048174.2(MUTYH):c.206G>A (p.Arg69Gln)]

NM_001048174.2(MUTYH):c.206G>A (p.Arg69Gln)

MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001048174.2(MUTYH):c.206G>A (p.Arg69Gln)
  • NC_000001.11:g.45333471C>T
  • NG_008189.1:g.12000G>A
  • NM_001048171.2:c.206G>A
  • NM_001048172.2:c.209G>A
  • NM_001048173.2:c.206G>A
  • NM_001048174.2:c.206G>AMANE SELECT
  • NM_001128425.1:c.290G>A
  • NM_001128425.2:c.290G>A
  • NM_001293190.2:c.251G>A
  • NM_001293191.2:c.239G>A
  • NM_001293192.2:c.-71G>A
  • NM_001293195.2:c.206G>A
  • NM_001293196.2:c.-71G>A
  • NM_001350650.2:c.-66G>A
  • NM_001350651.2:c.-66G>A
  • NM_012222.3:c.281G>A
  • NP_001041636.2:p.Arg69Gln
  • NP_001041637.1:p.Arg70Gln
  • NP_001041638.1:p.Arg69Gln
  • NP_001041639.1:p.Arg69Gln
  • NP_001121897.1:p.Arg97Gln
  • NP_001121897.1:p.Arg97Gln
  • NP_001280119.1:p.Arg84Gln
  • NP_001280120.1:p.Arg80Gln
  • NP_001280124.1:p.Arg69Gln
  • NP_036354.1:p.Arg94Gln
  • LRG_220t1:c.290G>A
  • LRG_220:g.12000G>A
  • LRG_220p1:p.Arg97Gln
  • NC_000001.10:g.45799143C>T
  • NC_000001.10:g.45799143C>T
  • NR_146882.2:n.434G>A
  • NR_146883.2:n.357G>A
  • p.R97Q
Protein change:
dbSNP: rs755653922
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001293192.2:c.-71G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001293196.2:c.-71G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001350650.2:c.-66G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001350651.2:c.-66G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001048171.2:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.2:c.209G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.2:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.2:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.1:c.290G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.2:c.290G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.2:c.251G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.2:c.239G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.2:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.3:c.281G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.2:n.434G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.2:n.357G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]


Hereditary cancer-predisposing syndrome
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000215643Ambry Geneticscriteria provided, single submitter
Uncertain significance
(Jan 2, 2019)
germlineclinical testing

Citation Link,

SCV000690551Color Health, Inccriteria provided, single submitter
Uncertain significance
(Feb 21, 2020)
germlineclinical testing

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


This missense variant replaces arginine with glutamine at codon 97 of the MUTYH protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 25186627). This variant has been identified in 3/251486 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.


Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing



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]

Details of each submission

From Ambry Genetics, SCV000215643.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided


The p.R97Q variant (also known as c.290G>A), located in coding exon 3 of the MUTYH gene, results from a G to A substitution at nucleotide position 290. The arginine at codon 97 is replaced by glutamine, an amino acid with highly similar properties. This alteration, designated as p.R94Q, has been detected in conjunction with a MUTYH founder mutation (phase unknown) in a patient diagnosed with early-onset colon cancer and bilateral breast cancer, as well as a family history of breast, colon, and uterine cancer, who had previously tested negative for mutations in BRCA1/2 by sequencing (Maxwell KN et al. Genet Med. 2015 Aug;17(8):630-8). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV000690551.3

#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: Oct 24, 2021

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