NM_001048174.2(MUTYH):c.1190A>G (p.Gln397Arg) AND Familial adenomatous polyposis 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 15, 2023
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:: RCV000821663.6

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1190A>G (p.Gln397Arg)]

NM_001048174.2(MUTYH):c.1190A>G (p.Gln397Arg)

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.1190A>G (p.Gln397Arg)

HGVS:

NC_000001.11:g.45331469T>C
NG_008189.1:g.14002A>G
NM_001048171.2:c.1190A>G
NM_001048172.2:c.1193A>G
NM_001048173.2:c.1190A>G
NM_001048174.2:c.1190A>GMANE SELECT
NM_001128425.2:c.1274A>G
NM_001293190.2:c.1235A>G
NM_001293191.2:c.1223A>G
NM_001293192.2:c.914A>G
NM_001293195.2:c.1190A>G
NM_001293196.2:c.914A>G
NM_001350650.2:c.845A>G
NM_001350651.2:c.845A>G
NM_012222.3:c.1265A>G
NP_001041636.2:p.Gln397Arg
NP_001041637.1:p.Gln398Arg
NP_001041638.1:p.Gln397Arg
NP_001041639.1:p.Gln397Arg
NP_001121897.1:p.Gln425Arg
NP_001121897.1:p.Gln425Arg
NP_001280119.1:p.Gln412Arg
NP_001280120.1:p.Gln408Arg
NP_001280121.1:p.Gln305Arg
NP_001280124.1:p.Gln397Arg
NP_001280125.1:p.Gln305Arg
NP_001337579.1:p.Gln282Arg
NP_001337580.1:p.Gln282Arg
NP_036354.1:p.Gln422Arg
LRG_220t1:c.1274A>G
LRG_220:g.14002A>G
LRG_220p1:p.Gln425Arg
NC_000001.10:g.45797141T>C
NM_001128425.1:c.1274A>G
NR_146882.2:n.1418A>G
NR_146883.2:n.1267A>G

Protein change:

Q282R

Links:

dbSNP: rs1205029214

NCBI 1000 Genomes Browser:

rs1205029214

Molecular consequence:

NM_001048171.2:c.1190A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.1193A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.1190A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.1190A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.1274A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.1235A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.1223A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001293192.2:c.914A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.1190A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001293196.2:c.914A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001350650.2:c.845A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001350651.2:c.845A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.1265A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.1418A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1267A>G - 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

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anoctamin-5b [Myxocyprinus asiaticus]
anoctamin-5b [Myxocyprinus asiaticus]
gi|2324529087|ref|XP_051558490.1|

Protein
Pancreatic ductal adenocarcinoma tumor and adjacent non-tumor tissue
Pancreatic ductal adenocarcinoma tumor and adjacent non-tumor tissue
Accession: GDS4336

GEO DataSets
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000962432	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 3, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004198828	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 15, 2023)	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

SCV000962432

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 3, 2023)

germline

clinical testing

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

SCV004198828

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 15, 2023)

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

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000962432.4

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

Description

This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 425 of the MUTYH protein (p.Gln425Arg). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 619702). 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 arginine 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, SCV004198828.1

#	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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