NM_001048171.1(MUTYH):c.451G>A (p.Ala151Thr) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Aug 12, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000590519.3

Allele description [Variation Report for NM_001048171.1(MUTYH):c.451G>A (p.Ala151Thr)]

NM_001048171.1(MUTYH):c.451G>A (p.Ala151Thr)

Gene:
MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_001048171.1(MUTYH):c.451G>A (p.Ala151Thr)
HGVS:
  • NC_000001.11:g.45332929C>T
  • NG_008189.1:g.12542G>A
  • NM_001048171.1:c.451G>A
  • NM_001048172.1:c.412G>A
  • NM_001048173.1:c.409G>A
  • NM_001048174.1:c.409G>A
  • NM_001128425.1:c.493G>A
  • NM_001293190.1:c.454G>A
  • NM_001293191.1:c.442G>A
  • NM_001293192.1:c.133G>A
  • NM_001293195.1:c.409G>A
  • NM_001293196.1:c.133G>A
  • NM_001350650.1:c.64G>A
  • NM_001350651.1:c.64G>A
  • NM_012222.2:c.484G>A
  • NP_001041636.1:p.Ala151Thr
  • NP_001041637.1:p.Ala138Thr
  • NP_001041638.1:p.Ala137Thr
  • NP_001041639.1:p.Ala137Thr
  • NP_001121897.1:p.Ala165Thr
  • NP_001280119.1:p.Ala152Thr
  • NP_001280120.1:p.Ala148Thr
  • NP_001280121.1:p.Ala45Thr
  • NP_001280124.1:p.Ala137Thr
  • NP_001280125.1:p.Ala45Thr
  • NP_001337579.1:p.Ala22Thr
  • NP_001337580.1:p.Ala22Thr
  • NP_036354.1:p.Ala162Thr
  • LRG_220t1:c.493G>A
  • LRG_220:g.12542G>A
  • LRG_220p1:p.Ala165Thr
  • NC_000001.10:g.45798601C>T
  • NR_146882.1:n.667G>A
  • NR_146883.1:n.481G>A
  • p.A165T
Protein change:
A137T
Links:
dbSNP: rs201103359
NCBI 1000 Genomes Browser:
rs201103359
Molecular consequence:
  • NM_001048171.1:c.451G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.1:c.412G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.1:c.409G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.1:c.409G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.1:c.493G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.1:c.454G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.1:c.442G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293192.1:c.133G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.1:c.409G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293196.1:c.133G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350650.1:c.64G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350651.1:c.64G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.2:c.484G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.1:n.667G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.1:n.481G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000697698Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Nov 25, 2016)
germlineclinical testing

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV001875080GeneDxcriteria provided, single submitter
Uncertain significance
(Aug 12, 2021)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697698.1

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

Description

Variant summary: The c.493G>A (p.Ala165Thr) in MUTYH gene is a missense change that involves a conserved nucleotide and 4/4 in silico tools predict deleterious outcome. The variant of interest is located within the HhH-GPD domain, however, the functional impact of this missense change is yet to be studied. The variant is present in the large control population dataset of ExAC at a frequency 0.00005 (6/121048 chrs tested), which does not exceed the estimated maximal expected allele frequency of a pathogenic variant in this gene (0.0056). The variant has not, to our knowledge, been reported in affected individuals. In addition, several reputable databases/clinical laboratories cite the variant as VUS. At this time there is not sufficient undeniable evidence to classify this variant with confidence. Taken together, the variant was classified as VUS until more data becomes available.

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

From GeneDx, SCV001875080.1

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

Description

In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Observed in individuals with kidney or breast cancer (Lu 2015, Tung 2015, Yehia 2018); This variant is associated with the following publications: (PMID: 31159747, 29684080, 28706299, 25186627, 26689913)

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

Last Updated: Sep 23, 2021

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