NM_001048171.1(MUTYH):c.995C>T (p.Ser332Leu) AND not specified

Clinical significance:Uncertain significance (Last evaluated: May 26, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_001048171.1(MUTYH):c.995C>T (p.Ser332Leu)]

NM_001048171.1(MUTYH):c.995C>T (p.Ser332Leu)

MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001048171.1(MUTYH):c.995C>T (p.Ser332Leu)
  • NC_000001.11:g.45331810G>A
  • NG_008189.1:g.13661C>T
  • NM_001048171.1:c.995C>T
  • NM_001048172.1:c.956C>T
  • NM_001048173.1:c.953C>T
  • NM_001048174.1:c.953C>T
  • NM_001128425.1:c.1037C>T
  • NM_001293190.1:c.998C>T
  • NM_001293191.1:c.986C>T
  • NM_001293192.1:c.677C>T
  • NM_001293195.1:c.953C>T
  • NM_001293196.1:c.677C>T
  • NM_001350650.1:c.608C>T
  • NM_001350651.1:c.608C>T
  • NM_012222.2:c.1028C>T
  • NP_001041636.1:p.Ser332Leu
  • NP_001041637.1:p.Ser319Leu
  • NP_001041638.1:p.Ser318Leu
  • NP_001041639.1:p.Ser318Leu
  • NP_001121897.1:p.Ser346Leu
  • NP_001280119.1:p.Ser333Leu
  • NP_001280120.1:p.Ser329Leu
  • NP_001280121.1:p.Ser226Leu
  • NP_001280124.1:p.Ser318Leu
  • NP_001280125.1:p.Ser226Leu
  • NP_001337579.1:p.Ser203Leu
  • NP_001337580.1:p.Ser203Leu
  • NP_036354.1:p.Ser343Leu
  • LRG_220t1:c.1037C>T
  • LRG_220:g.13661C>T
  • LRG_220p1:p.Ser346Leu
  • NC_000001.10:g.45797482G>A
  • NR_146882.1:n.1211C>T
  • NR_146883.1:n.1025C>T
Protein change:
dbSNP: rs587778538
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001048171.1:c.995C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.1:c.956C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.1:c.953C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.1:c.953C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.1:c.1037C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.1:c.998C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.1:c.986C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293192.1:c.677C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.1:c.953C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293196.1:c.677C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350650.1:c.608C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350651.1:c.608C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.2:c.1028C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.1:n.1211C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.1:n.1025C>T - 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)
SCV000085791ITMIno assertion providednot providedgermlinereference population

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

SCV001370687Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(May 26, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link


Please see associated publication for description of ethnicities


Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
Africangermlineunknownnot providednot providednot provided43not providedreference population
African_Europeangermlineunknownnot providednot providednot provided46not providedreference population
Central_Asiangermlineunknownnot providednot providednot provided50not providedreference population
East_Asiangermlineunknownnot providednot providednot provided62not providedreference population
Europeangermlineunknownnot providednot providednot provided331not providedreference population
Hispanicgermlineunknownnot providednot providednot provided118not providedreference population
Whole_cohortgermlineunknownnot providednot providednot provided681not providedreference population



Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

Bodian DL, McCutcheon JN, Kothiyal P, Huddleston KC, Iyer RK, Vockley JG, Niederhuber JE.

PLoS One. 2014;9(4):e94554. doi: 10.1371/journal.pone.0094554.

PubMed [citation]

Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.

Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P, Roa BB, Wenstrup RJ, Hartman AR, Syngal S.

Gastroenterology. 2015 Sep;149(3):604-13.e20. doi: 10.1053/j.gastro.2015.05.006. Epub 2015 May 14.

PubMed [citation]
See all PubMed Citations (4)

Details of each submission

From ITMI, SCV000085791.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Africannot providednot providednot providedreference population PubMed (1)
2African_Europeannot providednot providednot providedreference population PubMed (1)
3Central_Asiannot providednot providednot providedreference population PubMed (1)
4East_Asiannot providednot providednot providedreference population PubMed (1)
5Europeannot providednot providednot providedreference population PubMed (1)
6Hispanicnot providednot providednot providedreference population PubMed (1)
7Whole_cohortnot providednot providednot providedreference population PubMed (1)
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown43not provideddiscoverynot provided0not providednot provided
2germlineunknown46not provideddiscoverynot provided0not providednot provided
3germlineunknown50not provideddiscoverynot provided0not providednot provided
4germlineunknown62not provideddiscoverynot provided0not providednot provided
5germlineunknown331not provideddiscoverynot provided0.0015not providednot provided
6germlineunknown118not provideddiscoverynot provided0not providednot provided
7germlineunknown681not provideddiscoverynot provided0.0007not providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001370687.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)


Variant summary: MUTYH c.1037C>T (p.Ser346Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.4e-05 in 241834 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in MUTYH causing MUTYH-associated Polyposis (5.4e-05 vs 0.0046), allowing no conclusion about variant significance. c.1037C>T has been reported in the literature in sequencing studies of individuals affected with and/or undergoing testing for breast cancer, colorectal cancer (example, Tung_2015, Yurgelun_2015, Wang_2019). These report(s) 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. Three 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.

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

Last Updated: Sep 29, 2021

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