NM_001048174.2(MUTYH):c.1483C>T (p.Arg495Cys) AND Familial adenomatous polyposis 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 14, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000229869.14

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1483C>T (p.Arg495Cys)]

NM_001048174.2(MUTYH):c.1483C>T (p.Arg495Cys)

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.1483C>T (p.Arg495Cys)

HGVS:

NC_000001.11:g.45329389G>A
NG_008189.1:g.16082C>T
NM_001048171.2:c.1483C>T
NM_001048172.2:c.1486C>T
NM_001048173.2:c.1483C>T
NM_001048174.2:c.1483C>TMANE SELECT
NM_001128425.2:c.1567C>T
NM_001293190.2:c.1528C>T
NM_001293191.2:c.1516C>T
NM_001293192.2:c.1207C>T
NM_001293195.2:c.1483C>T
NM_001293196.2:c.1207C>T
NM_001350650.2:c.1138C>T
NM_001350651.2:c.1138C>T
NM_012222.3:c.1558C>T
NP_001041636.2:p.Arg495Cys
NP_001041637.1:p.Arg496Cys
NP_001041638.1:p.Arg495Cys
NP_001041639.1:p.Arg495Cys
NP_001121897.1:p.Arg523Cys
NP_001121897.1:p.Arg523Cys
NP_001280119.1:p.Arg510Cys
NP_001280120.1:p.Arg506Cys
NP_001280121.1:p.Arg403Cys
NP_001280124.1:p.Arg495Cys
NP_001280125.1:p.Arg403Cys
NP_001337579.1:p.Arg380Cys
NP_001337580.1:p.Arg380Cys
NP_036354.1:p.Arg520Cys
LRG_220t1:c.1567C>T
LRG_220:g.16082C>T
LRG_220p1:p.Arg523Cys
NC_000001.10:g.45795061G>A
NM_001128425.1:c.1567C>T
NR_146882.2:n.1891C>T
NR_146883.2:n.1740C>T
p.R523C

Protein change:

R380C

Links:

dbSNP: rs147480076

NCBI 1000 Genomes Browser:

rs147480076

Molecular consequence:

NM_001048171.2:c.1483C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.1486C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.1483C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.1483C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.1567C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.1528C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.1516C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293192.2:c.1207C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.1483C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293196.2:c.1207C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350650.2:c.1138C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350651.2:c.1138C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.1558C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.1891C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1740C>T - 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
SCV000285938	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 30, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27829682, 34347074, 34371384, 28492532
SCV004198809	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 14, 2024)	unknown	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

SCV000285938

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 30, 2024)

germline

clinical testing

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

SCV004198809

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 14, 2024)

unknown

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
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

Germline Alterations in Patients With IBD-associated Colorectal Cancer.

Biscaglia G, Latiano A, Castellana S, Fontana R, Gentile A, Latiano T, Corritore G, Panza A, Nardella M, Martino G, Bossa F, Perri F, Mazza T, Andriulli A, Palmieri O.

Inflamm Bowel Dis. 2022 Mar 2;28(3):447-454. doi: 10.1093/ibd/izab195.

PubMed [citation]

PMID:: 34347074

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000285938.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 523 of the MUTYH protein (p.Arg523Cys). This variant is present in population databases (rs147480076, gnomAD 0.02%). This missense change has been observed in individual(s) with colon polyposis, colorectal cancer, breast cancer, ovarian cancer and/or pancreatic cancer (PMID: 27829682, 34347074, 34371384). This variant is also known as c.1525C>T (p.Arg509Cys). ClinVar contains an entry for this variant (Variation ID: 185573). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	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

From Baylor Genetics, SCV004198809.2

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

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

Last Updated: Oct 13, 2024

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