NM_001048174.2(MUTYH):c.3G>A (p.Met1Ile) AND Familial adenomatous polyposis 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 28, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000803702.8

Allele description [Variation Report for NM_001048174.2(MUTYH):c.3G>A (p.Met1Ile)]

NM_001048174.2(MUTYH):c.3G>A (p.Met1Ile)

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.3G>A (p.Met1Ile)

HGVS:

NC_000001.11:g.45334503C>T
NG_008189.1:g.10968G>A
NM_001048171.2:c.3G>A
NM_001048172.2:c.3G>A
NM_001048173.2:c.3G>A
NM_001048174.2:c.3G>AMANE SELECT
NM_001128425.2:c.45G>A
NM_001293190.2:c.45G>A
NM_001293191.2:c.3G>A
NM_001293192.2:c.-210G>A
NM_001293195.2:c.3G>A
NM_001293196.2:c.-210G>A
NM_001350650.2:c.-269G>A
NM_001350651.2:c.-205G>A
NM_012222.3:c.45G>A
NP_001041636.2:p.Met1Ile
NP_001041637.1:p.Met1Ile
NP_001041638.1:p.Met1Ile
NP_001041639.1:p.Met1Ile
NP_001121897.1:p.Met15Ile
NP_001121897.1:p.Met15Ile
NP_001280119.1:p.Met15Ile
NP_001280120.1:p.Met1Ile
NP_001280124.1:p.Met1Ile
NP_036354.1:p.Met15Ile
LRG_220t1:c.45G>A
LRG_220:g.10968G>A
LRG_220p1:p.Met15Ile
NC_000001.10:g.45800175C>T
NM_001128425.1:c.45G>A
NR_146882.2:n.231G>A
NR_146883.2:n.154G>A

Protein change:

M15I

Links:

dbSNP: rs1570467004

NCBI 1000 Genomes Browser:

rs1570467004

Molecular consequence:

NM_001293192.2:c.-210G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001293196.2:c.-210G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350650.2:c.-269G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350651.2:c.-205G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001048171.2:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001048172.2:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001048173.2:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001048174.2:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001293191.2:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001293195.2:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001048171.2:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.45G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.45G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.45G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.231G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.154G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Bos taurus SAPS domain family, member 3, mRNA (cDNA clone MGC:166082 IMAGE:83252...
Bos taurus SAPS domain family, member 3, mRNA (cDNA clone MGC:166082 IMAGE:8325240), complete cds
gi|157279128|gb|BC153249.1|

Nucleotide
LOC132174998 [Corylus avellana]
LOC132174998 [Corylus avellana]
Gene ID:132174998

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000943585	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 28, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27829682, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000943585

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 28, 2018)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Type and frequency of MUTYH variants in Italian patients with suspected MAP: a retrospective multicenter study.

Ricci MT, Miccoli S, Turchetti D, Bondavalli D, Viel A, Quaia M, Giacomini E, Gismondi V, Sanchez-Mete L, Stigliano V, Martayan A, Mazzei F, Bignami M, Bonelli L, Varesco L.

J Hum Genet. 2017 Feb;62(2):309-315. doi: 10.1038/jhg.2016.132. Epub 2016 Nov 10.

PubMed [citation]

PMID:: 27829682

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000943585.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 15 of the MUTYH protein (p.Met15Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant has been observed in an individual affected with¬†colorectal cancer¬†(PMID: 27829682). 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. The¬†p.Met15¬†amino acid residue in MUTYH has been determined to be clinically significant (PMID:¬†24691292). This suggests that variants that disrupt this residue are likely to be causative of disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0").

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine