NM_001048174.2(MUTYH):c.1400G>A (p.Arg467His) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 27, 2019
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:: RCV000236240.10

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1400G>A (p.Arg467His)]

NM_001048174.2(MUTYH):c.1400G>A (p.Arg467His)

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.1400G>A (p.Arg467His)

HGVS:

NC_000001.11:g.45330550C>T
NG_008189.1:g.14921G>A
NM_001048171.2:c.1400G>A
NM_001048172.2:c.1403G>A
NM_001048173.2:c.1400G>A
NM_001048174.2:c.1400G>AMANE SELECT
NM_001128425.2:c.1484G>A
NM_001293190.2:c.1445G>A
NM_001293191.2:c.1433G>A
NM_001293192.2:c.1124G>A
NM_001293195.2:c.1400G>A
NM_001293196.2:c.1124G>A
NM_001350650.2:c.1055G>A
NM_001350651.2:c.1055G>A
NM_012222.3:c.1475G>A
NP_001041636.1:p.Arg481His
NP_001041636.2:p.Arg467His
NP_001041637.1:p.Arg468His
NP_001041638.1:p.Arg467His
NP_001041639.1:p.Arg467His
NP_001121897.1:p.Arg495His
NP_001121897.1:p.Arg495His
NP_001280119.1:p.Arg482His
NP_001280120.1:p.Arg478His
NP_001280121.1:p.Arg375His
NP_001280124.1:p.Arg467His
NP_001280125.1:p.Arg375His
NP_001337579.1:p.Arg352His
NP_001337580.1:p.Arg352His
NP_036354.1:p.Arg492His
LRG_220t1:c.1484G>A
LRG_220:g.14921G>A
LRG_220p1:p.Arg495His
NC_000001.10:g.45796222C>T
NM_001048171.1:c.1442G>A
NM_001128425.1:c.1484G>A
NR_146882.2:n.1628G>A
NR_146883.2:n.1477G>A
p.R495H

Protein change:

R352H

Links:

dbSNP: rs144111588

NCBI 1000 Genomes Browser:

rs144111588

Molecular consequence:

NM_001048171.2:c.1400G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.1403G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.1400G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.1400G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.1484G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.1445G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.1433G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293192.2:c.1124G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.1400G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293196.2:c.1124G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350650.2:c.1055G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350651.2:c.1055G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.1475G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.1628G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1477G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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RecName: Full=Electron transfer flavoprotein subunit alpha, mitochondrial; Short...
RecName: Full=Electron transfer flavoprotein subunit alpha, mitochondrial; Short=Alpha-ETF; Flags: Precursor
gi|146345417|sp|Q99LC5.2|ETFA_MOUSE

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000917799	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Nov 24, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26694661, 27443514 Citation Link,
SCV002067820	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 27, 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

SCV000917799

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Nov 24, 2017)

germline

clinical testing

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

Citation Link,

SCV002067820

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 27, 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	no	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

Functional Evaluation of Nine Missense-Type Variants of the Human DNA Glycosylase Enzyme MUTYH in the Japanese Population.

Shinmura K, Kato H, Goto M, Yamada H, Tao H, Nakamura S, Sugimura H.

Hum Mutat. 2016 Apr;37(4):350-3. doi: 10.1002/humu.22949. Epub 2016 Jan 8.

PubMed [citation]

PMID:: 26694661

Germline multi-gene hereditary cancer panel testing in an unselected endometrial cancer cohort.

Ring KL, Bruegl AS, Allen BA, Elkin EP, Singh N, Hartman AR, Daniels MS, Broaddus RR.

Mod Pathol. 2016 Nov;29(11):1381-1389. doi: 10.1038/modpathol.2016.135. Epub 2016 Jul 22.

PubMed [citation]

PMID:: 27443514
PMCID:: PMC5541389

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917799.1

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

Description

Variant summary: The MUTYH c.1484G>A (p.Arg495His) variant involves the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 9/267106 control chromosomes at a frequency of 0.0000337, which does not exceed the estimated maximal expected allele frequency of a pathogenic MUTYH variant (0.0055902). The variant has been reported in Lynch Syndrome patients in the literature, one in the tumor of a patient who carried a likely pathogenic MSH2 germline variant, as well as in the germline of a patient carrying a pathogenic MSH6 variant (Vargas-Parra_2017, Ring_2016). However, due to the predominantly recessive mode of inheritance attributed to variants in MUTYH, the possibility of incidental carrier status for a pathogenic variant cannot be excluded. The DNA glycosylase activity and ability to suppress mutations caused by 8-hydroxyguanine, an oxidized form of guanine, were examined for the nine variants of type 2 MUTYH, a nuclear form of the enzyme, by DNA cleavage activity assay and supF forward mutation assay, respectively. The variant was similar to WT in DNA glycosylase activity and mutation frequency of the supF gene. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, this variant is classified as VUS.

#	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 Genetic Services Laboratory, University of Chicago, SCV002067820.1

#	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	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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