NM_001048174.2(MUTYH):c.900C>A (p.Asp300Glu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 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:: RCV000562155.8

Allele description [Variation Report for NM_001048174.2(MUTYH):c.900C>A (p.Asp300Glu)]

NM_001048174.2(MUTYH):c.900C>A (p.Asp300Glu)

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.900C>A (p.Asp300Glu)

HGVS:

NC_000001.11:g.45332036G>T
NG_008189.1:g.13435C>A
NM_001048171.2:c.900C>A
NM_001048172.2:c.903C>A
NM_001048173.2:c.900C>A
NM_001048174.2:c.900C>AMANE SELECT
NM_001128425.2:c.984C>A
NM_001293190.2:c.945C>A
NM_001293191.2:c.933C>A
NM_001293192.2:c.624C>A
NM_001293195.2:c.900C>A
NM_001293196.2:c.624C>A
NM_001350650.2:c.555C>A
NM_001350651.2:c.555C>A
NM_012222.3:c.975C>A
NP_001041636.2:p.Asp300Glu
NP_001041637.1:p.Asp301Glu
NP_001041638.1:p.Asp300Glu
NP_001041639.1:p.Asp300Glu
NP_001121897.1:p.Asp328Glu
NP_001121897.1:p.Asp328Glu
NP_001280119.1:p.Asp315Glu
NP_001280120.1:p.Asp311Glu
NP_001280121.1:p.Asp208Glu
NP_001280124.1:p.Asp300Glu
NP_001280125.1:p.Asp208Glu
NP_001337579.1:p.Asp185Glu
NP_001337580.1:p.Asp185Glu
NP_036354.1:p.Asp325Glu
LRG_220t1:c.984C>A
LRG_220:g.13435C>A
LRG_220p1:p.Asp328Glu
NC_000001.10:g.45797708G>T
NM_001128425.1:c.984C>A
NR_146882.2:n.1128C>A
NR_146883.2:n.977C>A

Protein change:

D185E

Links:

dbSNP: rs587780752

NCBI 1000 Genomes Browser:

rs587780752

Molecular consequence:

NM_001048171.2:c.900C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.903C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.900C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.900C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.984C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.945C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.933C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293192.2:c.624C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.900C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293196.2:c.624C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350650.2:c.555C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350651.2:c.555C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.975C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.1128C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.977C>A - 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
SCV000670161	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (May 24, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000685682	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 29, 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

SCV000670161

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(May 24, 2023)

germline

clinical testing

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

Citation Link,

SCV000685682

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 29, 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

Targeted sequencing of 36 known or putative colorectal cancer susceptibility genes.

DeRycke MS, Gunawardena S, Balcom JR, Pickart AM, Waltman LA, French AJ, McDonnell S, Riska SM, Fogarty ZC, Larson MC, Middha S, Eckloff BW, Asmann YW, Ferber MJ, Haile RW, Gallinger S, Clendenning M, Rosty C, Win AK, Buchanan DD, Hopper JL, Newcomb PA, et al.

Mol Genet Genomic Med. 2017 Sep;5(5):553-569. doi: 10.1002/mgg3.317.

PubMed [citation]

PMID:: 28944238
PMCID:: PMC5606870

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, SCV000670161.6

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

Description

The p.D328E variant (also known as c.984C>A), located in coding exon 11 of the MUTYH gene, results from a C to A substitution at nucleotide position 984. The aspartic acid at codon 328 is replaced by glutamic acid, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with colorectal cancer (DeRycke MS et al. Mol Genet Genomic Med, 2017 Sep;5:553-569). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated 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, SCV000685682.3

#	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: May 7, 2024

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