NM_001048174.2(MUTYH):c.1120T>C (p.Trp374Arg) AND Familial adenomatous polyposis 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 25, 2020
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:: RCV001309790.7

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1120T>C (p.Trp374Arg)]

NM_001048174.2(MUTYH):c.1120T>C (p.Trp374Arg)

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.1120T>C (p.Trp374Arg)

HGVS:

NC_000001.11:g.45331539A>G
NG_008189.1:g.13932T>C
NM_001048171.2:c.1120T>C
NM_001048172.2:c.1123T>C
NM_001048173.2:c.1120T>C
NM_001048174.2:c.1120T>CMANE SELECT
NM_001128425.2:c.1204T>C
NM_001293190.2:c.1165T>C
NM_001293191.2:c.1153T>C
NM_001293192.2:c.844T>C
NM_001293195.2:c.1120T>C
NM_001293196.2:c.844T>C
NM_001350650.2:c.775T>C
NM_001350651.2:c.775T>C
NM_012222.3:c.1195T>C
NP_001041636.2:p.Trp374Arg
NP_001041637.1:p.Trp375Arg
NP_001041638.1:p.Trp374Arg
NP_001041639.1:p.Trp374Arg
NP_001121897.1:p.Trp402Arg
NP_001280119.1:p.Trp389Arg
NP_001280120.1:p.Trp385Arg
NP_001280121.1:p.Trp282Arg
NP_001280124.1:p.Trp374Arg
NP_001280125.1:p.Trp282Arg
NP_001337579.1:p.Trp259Arg
NP_001337580.1:p.Trp259Arg
NP_036354.1:p.Trp399Arg
LRG_220:g.13932T>C
NC_000001.10:g.45797211A>G
NR_146882.2:n.1348T>C
NR_146883.2:n.1197T>C

Protein change:

W259R

Links:

dbSNP: rs1644859886

NCBI 1000 Genomes Browser:

rs1644859886

Molecular consequence:

NM_001048171.2:c.1120T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.1123T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.1120T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.1120T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.1204T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.1165T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.1153T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293192.2:c.844T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.1120T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293196.2:c.844T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001350650.2:c.775T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001350651.2:c.775T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.1195T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.1348T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1197T>C - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001499299	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 25, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001499299

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 25, 2020)

germline

clinical testing

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

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

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, SCV001499299.4

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

Description

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. 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. This variant has not been reported in the literature in individuals with MUTYH-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tryptophan with arginine at codon 402 of the MUTYH protein (p.Trp402Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine.

#	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

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