NM_001048171.1(MUTYH):c.451G>A (p.Ala151Thr) AND MYH-associated polyposis

Clinical significance:Uncertain significance (Last evaluated: Aug 9, 2020)

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:
RCV000228243.8

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)

Name:
MYH-associated polyposis (FAP2)
Synonyms:
COLORECTAL ADENOMATOUS POLYPOSIS, AUTOSOMAL RECESSIVE; ADENOMAS, MULTIPLE COLORECTAL, AUTOSOMAL RECESSIVE; FAP type 2; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0012041; MedGen: C3272841; Orphanet: 220460; OMIM: 608456

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000285952Invitaecriteria provided, single submitter
Uncertain significance
(Aug 9, 2020)
germlineclinical testing

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

SCV000792228Counsylcriteria provided, single submitter
Uncertain significance
(Jun 13, 2017)
unknownclinical 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
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations.

Tsaousis GN, Papadopoulou E, Apessos A, Agiannitopoulos K, Pepe G, Kampouri S, Diamantopoulos N, Floros T, Iosifidou R, Katopodi O, Koumarianou A, Markopoulos C, Papazisis K, Venizelos V, Xanthakis I, Xepapadakis G, Banu E, Eniu DT, Negru S, Stanculeanu DL, Ungureanu A, Ozmen V, et al.

BMC Cancer. 2019 Jun 3;19(1):535. doi: 10.1186/s12885-019-5756-4.

PubMed [citation]
PMID:
31159747
PMCID:
PMC6547505

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000285952.8

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

Description

This sequence change replaces alanine with threonine at codon 165 of the MUTYH protein (p.Ala165Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs201103359, ExAC 0.05%). This variant has been observed in individual(s) undergoing multigene testing for hereditary cancer (PMID: 31159747). ClinVar contains an entry for this variant (Variation ID: 185959). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

From Counsyl, SCV000792228.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 23, 2021

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