NM_001048174.2(MUTYH):c.763A>G (p.Met255Val) AND MYH-associated polyposis

Clinical significance:Likely pathogenic (Last evaluated: Dec 11, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000536194.4

Allele description [Variation Report for NM_001048174.2(MUTYH):c.763A>G (p.Met255Val)]

NM_001048174.2(MUTYH):c.763A>G (p.Met255Val)

Gene:
MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_001048174.2(MUTYH):c.763A>G (p.Met255Val)
HGVS:
  • NC_000001.11:g.45332252T>C
  • NG_008189.1:g.13219A>G
  • NM_001048171.2:c.763A>G
  • NM_001048172.2:c.766A>G
  • NM_001048173.2:c.763A>G
  • NM_001048174.2:c.763A>GMANE SELECT
  • NM_001128425.1:c.847A>G
  • NM_001128425.2:c.847A>G
  • NM_001293190.2:c.808A>G
  • NM_001293191.2:c.796A>G
  • NM_001293192.2:c.487A>G
  • NM_001293195.2:c.763A>G
  • NM_001293196.2:c.487A>G
  • NM_001350650.2:c.418A>G
  • NM_001350651.2:c.418A>G
  • NM_012222.3:c.838A>G
  • NP_001041636.2:p.Met255Val
  • NP_001041637.1:p.Met256Val
  • NP_001041638.1:p.Met255Val
  • NP_001041639.1:p.Met255Val
  • NP_001121897.1:p.Met283Val
  • NP_001121897.1:p.Met283Val
  • NP_001280119.1:p.Met270Val
  • NP_001280120.1:p.Met266Val
  • NP_001280121.1:p.Met163Val
  • NP_001280124.1:p.Met255Val
  • NP_001280125.1:p.Met163Val
  • NP_001337579.1:p.Met140Val
  • NP_001337580.1:p.Met140Val
  • NP_036354.1:p.Met280Val
  • LRG_220t1:c.847A>G
  • LRG_220:g.13219A>G
  • LRG_220p1:p.Met283Val
  • NC_000001.10:g.45797924T>C
  • NR_146882.2:n.991A>G
  • NR_146883.2:n.840A>G
Protein change:
M140V
Links:
dbSNP: rs876659676
NCBI 1000 Genomes Browser:
rs876659676
Molecular consequence:
  • NM_001048171.2:c.763A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.2:c.766A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.2:c.763A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.2:c.763A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.1:c.847A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.2:c.847A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.2:c.808A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.2:c.796A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293192.2:c.487A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.2:c.763A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293196.2:c.487A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350650.2:c.418A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350651.2:c.418A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.3:c.838A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.2:n.991A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.2:n.840A>G - 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
SCV000639358Invitaecriteria provided, single submitter
Likely pathogenic
(Dec 11, 2018)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Adenine DNA glycosylase activity of 14 human MutY homolog (MUTYH) variant proteins found in patients with colorectal polyposis and cancer.

Goto M, Shinmura K, Nakabeppu Y, Tao H, Yamada H, Tsuneyoshi T, Sugimura H.

Hum Mutat. 2010 Nov;31(11):E1861-74. doi: 10.1002/humu.21363.

PubMed [citation]
PMID:
20848659
PMCID:
PMC3051265

Identification of patients with (atypical) MUTYH-associated polyposis by KRAS2 c.34G > T prescreening followed by MUTYH hotspot analysis in formalin-fixed paraffin-embedded tissue.

van Puijenbroek M, Nielsen M, Tops CM, Halfwerk H, Vasen HF, Weiss MM, van Wezel T, Hes FJ, Morreau H.

Clin Cancer Res. 2008 Jan 1;14(1):139-42. doi: 10.1158/1078-0432.CCR-07-1705.

PubMed [citation]
PMID:
18172263
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000639358.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces methionine with valine at codon 283 of the MUTYH protein (p.Met283Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to co-occur with another MUTYH variant in individuals affected with MUTYH-associated polyposis including evidence of segregation in one family (PMID: 18172263, 16941501). ClinVar contains an entry for this variant (Variation ID: 232291). Experimental studies have shown that this missense change impairs the glycosylase activity and the suppression of oxidative mutagenesis activity of the encoded protein (PMID: 20848659, 23322991). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 25, 2021

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