NM_001048171.1(MUTYH):c.1033C>A (p.Pro345Thr) AND MYH-associated polyposis

Clinical significance:Uncertain significance (Last evaluated: Oct 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:
current
Accession:
RCV000411922.7

Allele description [Variation Report for NM_001048171.1(MUTYH):c.1033C>A (p.Pro345Thr)]

NM_001048171.1(MUTYH):c.1033C>A (p.Pro345Thr)

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.1033C>A (p.Pro345Thr)
HGVS:
  • NC_000001.11:g.45331772G>T
  • NG_008189.1:g.13699C>A
  • NM_001048171.1:c.1033C>A
  • NM_001048172.1:c.994C>A
  • NM_001048173.1:c.991C>A
  • NM_001048174.1:c.991C>A
  • NM_001128425.1:c.1075C>A
  • NM_001293190.1:c.1036C>A
  • NM_001293191.1:c.1024C>A
  • NM_001293192.1:c.715C>A
  • NM_001293195.1:c.991C>A
  • NM_001293196.1:c.715C>A
  • NM_001350650.1:c.646C>A
  • NM_001350651.1:c.646C>A
  • NM_012222.2:c.1066C>A
  • NP_001041636.1:p.Pro345Thr
  • NP_001041637.1:p.Pro332Thr
  • NP_001041638.1:p.Pro331Thr
  • NP_001041639.1:p.Pro331Thr
  • NP_001121897.1:p.Pro359Thr
  • NP_001280119.1:p.Pro346Thr
  • NP_001280120.1:p.Pro342Thr
  • NP_001280121.1:p.Pro239Thr
  • NP_001280124.1:p.Pro331Thr
  • NP_001280125.1:p.Pro239Thr
  • NP_001337579.1:p.Pro216Thr
  • NP_001337580.1:p.Pro216Thr
  • NP_036354.1:p.Pro356Thr
  • LRG_220t1:c.1075C>A
  • LRG_220:g.13699C>A
  • LRG_220p1:p.Pro359Thr
  • NC_000001.10:g.45797444G>T
  • NR_146882.1:n.1249C>A
  • NR_146883.1:n.1063C>A
  • p.P359T
Protein change:
P216T
Links:
dbSNP: rs587782773
NCBI 1000 Genomes Browser:
rs587782773
Molecular consequence:
  • NM_001048171.1:c.1033C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.1:c.994C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.1:c.991C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.1:c.991C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.1:c.1075C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.1:c.1036C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.1:c.1024C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293192.1:c.715C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.1:c.991C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293196.1:c.715C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350650.1:c.646C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350651.1:c.646C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.2:c.1066C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.1:n.1249C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.1:n.1063C>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
SCV000487368Counsylcriteria provided, single submitter
Uncertain significance
(Aug 8, 2016)
unknownclinical testing

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

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV000545747Invitaecriteria provided, single submitter
Uncertain significance
(Oct 21, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer.

Maxwell KN, Hart SN, Vijai J, Schrader KA, Slavin TP, Thomas T, Wubbenhorst B, Ravichandran V, Moore RM, Hu C, Guidugli L, Wenz B, Domchek SM, Robson ME, Szabo C, Neuhausen SL, Weitzel JN, Offit K, Couch FJ, Nathanson KL.

Am J Hum Genet. 2016 May 5;98(5):801-817. doi: 10.1016/j.ajhg.2016.02.024.

PubMed [citation]
PMID:
27153395
PMCID:
PMC4863474

MUTYH-associated polyposis--from defect in base excision repair to clinical genetic testing.

Cheadle JP, Sampson JR.

DNA Repair (Amst). 2007 Mar 1;6(3):274-9. Epub 2006 Dec 11. Review.

PubMed [citation]
PMID:
17161978
See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000487368.1

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

From Invitae, SCV000545747.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces proline with threonine at codon 359 of the MUTYH protein (p.Pro359Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs587782773, ExAC 0.005%). This variant has been observed in individuals with MUTYH-related disease (PMID: 17161978, 17581577, 28944238). It is also known as P345T in the literature. ClinVar contains an entry for this variant (Variation ID: 142860). 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. 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

Last Updated: Sep 29, 2021

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