NM_001048174.2(MUTYH):c.596C>T (p.Ala199Val) AND Familial adenomatous polyposis 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 27, 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:: RCV000475653.14

Allele description [Variation Report for NM_001048174.2(MUTYH):c.596C>T (p.Ala199Val)]

NM_001048174.2(MUTYH):c.596C>T (p.Ala199Val)

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.596C>T (p.Ala199Val)

HGVS:

NC_000001.11:g.45332584G>A
NG_008189.1:g.12887C>T
NM_001048171.2:c.596C>T
NM_001048172.2:c.599C>T
NM_001048173.2:c.596C>T
NM_001048174.2:c.596C>TMANE SELECT
NM_001128425.2:c.680C>T
NM_001293190.2:c.641C>T
NM_001293191.2:c.629C>T
NM_001293192.2:c.320C>T
NM_001293195.2:c.596C>T
NM_001293196.2:c.320C>T
NM_001350650.2:c.251C>T
NM_001350651.2:c.251C>T
NM_012222.3:c.671C>T
NP_001041636.2:p.Ala199Val
NP_001041637.1:p.Ala200Val
NP_001041638.1:p.Ala199Val
NP_001041639.1:p.Ala199Val
NP_001121897.1:p.Ala227Val
NP_001121897.1:p.Ala227Val
NP_001280119.1:p.Ala214Val
NP_001280120.1:p.Ala210Val
NP_001280121.1:p.Ala107Val
NP_001280124.1:p.Ala199Val
NP_001280125.1:p.Ala107Val
NP_001337579.1:p.Ala84Val
NP_001337580.1:p.Ala84Val
NP_036354.1:p.Ala224Val
LRG_220t1:c.680C>T
LRG_220:g.12887C>T
LRG_220p1:p.Ala227Val
NC_000001.10:g.45798256G>A
NM_001128425.1:c.680C>T
NR_146882.2:n.824C>T
NR_146883.2:n.673C>T

Protein change:

A107V

Links:

dbSNP: rs11545695

NCBI 1000 Genomes Browser:

rs11545695

Molecular consequence:

NM_001048171.2:c.596C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.599C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.596C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.596C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.680C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.641C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.629C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293192.2:c.320C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.596C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293196.2:c.320C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350650.2:c.251C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350651.2:c.251C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.671C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.824C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.673C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

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
SCV000545794	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 27, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25820570, 21520333, 28492532
SCV004841537	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (May 15, 2023)	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

SCV000545794

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 27, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004841537

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(May 15, 2023)

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	1	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Functional Complementation Assay for 47 MUTYH Variants in a MutY-Disrupted Escherichia coli Strain.

Komine K, Shimodaira H, Takao M, Soeda H, Zhang X, Takahashi M, Ishioka C.

Hum Mutat. 2015 Jul;36(7):704-11. doi: 10.1002/humu.22794.

PubMed [citation]

PMID:: 25820570
PMCID:: PMC4682456

LOVD v.2.0: the next generation in gene variant databases.

Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT.

Hum Mutat. 2011 May;32(5):557-63. doi: 10.1002/humu.21438. Epub 2011 Feb 22.

PubMed [citation]

PMID:: 21520333

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000545794.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on MUTYH function (PMID: 25820570). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 230300). This missense change has been observed in individual(s) with clinical features of MUTYH-related conditions (PMID: 21520333). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 227 of the MUTYH protein (p.Ala227Val).

#	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 All of Us Research Program, National Institutes of Health, SCV004841537.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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	germline	unknown	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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