NM_001048174.2(MUTYH):c.488G>A (p.Arg163Gln) AND Familial adenomatous polyposis 2

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Feb 19, 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:: RCV000168022.15

Allele description [Variation Report for NM_001048174.2(MUTYH):c.488G>A (p.Arg163Gln)]

NM_001048174.2(MUTYH):c.488G>A (p.Arg163Gln)

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.488G>A (p.Arg163Gln)

Other names:

p.R191Q:CGG>CAG

HGVS:

NC_000001.11:g.45332767C>T
NG_008189.1:g.12704G>A
NM_001048171.2:c.488G>A
NM_001048172.2:c.491G>A
NM_001048173.2:c.488G>A
NM_001048174.2:c.488G>AMANE SELECT
NM_001128425.2:c.572G>A
NM_001293190.2:c.533G>A
NM_001293191.2:c.521G>A
NM_001293192.2:c.212G>A
NM_001293195.2:c.488G>A
NM_001293196.2:c.212G>A
NM_001350650.2:c.143G>A
NM_001350651.2:c.143G>A
NM_012222.3:c.563G>A
NP_001041636.1:p.Arg177Gln
NP_001041636.2:p.Arg163Gln
NP_001041637.1:p.Arg164Gln
NP_001041638.1:p.Arg163Gln
NP_001041639.1:p.Arg163Gln
NP_001121897.1:p.Arg191Gln
NP_001121897.1:p.Arg191Gln
NP_001280119.1:p.Arg178Gln
NP_001280120.1:p.Arg174Gln
NP_001280121.1:p.Arg71Gln
NP_001280124.1:p.Arg163Gln
NP_001280125.1:p.Arg71Gln
NP_001337579.1:p.Arg48Gln
NP_001337580.1:p.Arg48Gln
NP_036354.1:p.Arg188Gln
LRG_220t1:c.572G>A
LRG_220:g.12704G>A
LRG_220p1:p.Arg191Gln
NC_000001.10:g.45798439C>T
NM_001048171.1:c.530G>A
NM_001128425.1:c.572G>A
NR_146882.2:n.716G>A
NR_146883.2:n.565G>A
p.R191Q

Protein change:

R163Q

Links:

dbSNP: rs369677603

NCBI 1000 Genomes Browser:

rs369677603

Molecular consequence:

NM_001048171.2:c.488G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.491G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.488G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.488G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.572G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.533G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.521G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293192.2:c.212G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.488G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293196.2:c.212G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350650.2:c.143G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350651.2:c.143G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.563G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.716G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.565G>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000218674	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 29, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31159747, 28492532
SCV000799307	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Apr 9, 2018)	unknown	clinical testing	Citation Link,
SCV004198805	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 19, 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

SCV000218674

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 29, 2024)

germline

clinical testing

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

SCV000799307

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Apr 9, 2018)

unknown

clinical testing

Citation Link,

SCV004198805

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 19, 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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations.

Tsaousis GN, Papadopoulou E, Apessos A, Agiannitopoulos K, Pepe G, Kampouri S, Diamantopoulos N, Floros T, Iosifidou R, Katopodi O, Koumarianou A, Markopoulos C, Papazisis K, Venizelos V, Xanthakis I, Xepapadakis G, Banu E, Eniu DT, Negru S, Stanculeanu DL, Ungureanu A, Ozmen V, et al.

BMC Cancer. 2019 Jun 3;19(1):535. doi: 10.1186/s12885-019-5756-4.

PubMed [citation]

PMID:: 31159747
PMCID:: PMC6547505

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000218674.12

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

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 191 of the MUTYH protein (p.Arg191Gln). This variant is present in population databases (rs369677603, gnomAD 0.1%). This missense change has been observed in individual(s) with clinical features of MUTYH-related conditions (PMID: 31159747). ClinVar contains an entry for this variant (Variation ID: 127846). 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 glutamine 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 Counsyl, SCV000799307.1

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

#	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

From Baylor Genetics, SCV004198805.2

#	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: Sep 29, 2024

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