NM_001048174.2(MUTYH):c.596C>T (p.Ala199Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 24, 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:: RCV000218668.9

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]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000273794	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 24, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000685657	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 21, 2019)	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

SCV000273794

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 24, 2023)

germline

clinical testing

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

Citation Link,

SCV000685657

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 21, 2019)

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

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

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 Ambry Genetics, SCV000273794.8

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

Description

The p.A227V variant (also known as c.680C>T), located in coding exon 8 of the MUTYH gene, results from a C to T substitution at nucleotide position 680. The alanine at codon 227 is replaced by valine, an amino acid with similar properties. In a study assessing the base excision repair capabilities of several MUTYH variants, this alteration was found to be partially defective (Komine K et al. Hum. Mutat. 2015 Jul;36:704-11). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 Color Diagnostics, LLC DBA Color Health, SCV000685657.3

#	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	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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