NM_001128425.1(MUTYH):c.1000C>G (p.Pro334Ala) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Mar 30, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_001128425.1(MUTYH):c.1000C>G (p.Pro334Ala)]

NM_001128425.1(MUTYH):c.1000C>G (p.Pro334Ala)

MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001128425.1(MUTYH):c.1000C>G (p.Pro334Ala)
  • NC_000001.11:g.45331847G>C
  • NG_008189.1:g.13624C>G
  • NM_001048171.1:c.958C>G
  • NM_001048172.1:c.919C>G
  • NM_001048173.1:c.916C>G
  • NM_001048174.1:c.916C>G
  • NM_001128425.1:c.1000C>G
  • NM_001293190.1:c.961C>G
  • NM_001293191.1:c.949C>G
  • NM_001293192.1:c.640C>G
  • NM_001293195.1:c.916C>G
  • NM_001293196.1:c.640C>G
  • NM_001350650.1:c.571C>G
  • NM_001350651.1:c.571C>G
  • NM_012222.2:c.991C>G
  • NP_001041636.1:p.Pro320Ala
  • NP_001041637.1:p.Pro307Ala
  • NP_001041638.1:p.Pro306Ala
  • NP_001041639.1:p.Pro306Ala
  • NP_001121897.1:p.Pro334Ala
  • NP_001280119.1:p.Pro321Ala
  • NP_001280120.1:p.Pro317Ala
  • NP_001280121.1:p.Pro214Ala
  • NP_001280124.1:p.Pro306Ala
  • NP_001280125.1:p.Pro214Ala
  • NP_001337579.1:p.Pro191Ala
  • NP_001337580.1:p.Pro191Ala
  • NP_036354.1:p.Pro331Ala
  • LRG_220t1:c.1000C>G
  • LRG_220:g.13624C>G
  • LRG_220p1:p.Pro334Ala
  • NC_000001.10:g.45797519G>C
  • NR_146882.1:n.1174C>G
  • NR_146883.1:n.988C>G
  • p.P334A
Protein change:
dbSNP: rs587778537
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001048171.1:c.958C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.1:c.919C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.1:c.916C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.1:c.916C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.1:c.1000C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.1:c.961C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.1:c.949C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293192.1:c.640C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.1:c.916C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293196.1:c.640C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350650.1:c.571C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350651.1:c.571C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.2:c.991C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.1:n.1174C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.1:n.988C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]


MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000917801Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Mar 30, 2018)
germlineclinical testing

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

Citation Link

Summary from all submissions

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



Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

Yurgelun MB, Kulke MH, Fuchs CS, Allen BA, Uno H, Hornick JL, Ukaegbu CI, Brais LK, McNamara PG, Mayer RJ, Schrag D, Meyerhardt JA, Ng K, Kidd J, Singh N, Hartman AR, Wenstrup RJ, Syngal S.

J Clin Oncol. 2017 Apr 1;35(10):1086-1095. doi: 10.1200/JCO.2016.71.0012. Epub 2017 Jan 30.

PubMed [citation]

Prevalence and characteristics of MUTYH-associated polyposis in patients with multiple adenomatous and serrated polyps.

Guarinos C, Juárez M, Egoavil C, Rodríguez-Soler M, Pérez-Carbonell L, Salas R, Cubiella J, Rodríguez-Moranta F, de-Castro L, Bujanda L, Serradesanferm A, Nicolás-Pérez D, Herráiz M, Fernández-Bañares F, Herreros-de-Tejada A, Aguirre E, Balmaña J, Rincón ML, Pizarro A, Polo-Ortiz F, Castillejo A, Alenda C, et al.

Clin Cancer Res. 2014 Mar 1;20(5):1158-68. doi: 10.1158/1078-0432.CCR-13-1490. Epub 2014 Jan 27.

PubMed [citation]

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917801.1

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


Variant summary: MUTYH c.1000C>G (p.Pro334Ala) results in a non-conservative amino acid change in the encoded protein sequence that lies 3 nucleotides away from an exon-intron junction. Four of five in-silico tools predict a benign effect of the variant on protein function. 4/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.3e-05 in 224868 control chromosomes. This frequency is not higher than expected for a pathogenic variant in MUTYH causing MUTYH-associated Polyposis (1.3e-05 vs 0.0046), allowing no conclusion about variant significance. c.1000C>G has been reported in the literature in individuals affected with MUTYH-associated Polyposis. However, these reports do not provide unequivocal conclusions about an association of the variant with MUTYH-associated Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and both classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Aug 5, 2021

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