NM_001048174.2(MUTYH):c.1217C>T (p.Thr406Met) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Jun 4, 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:: RCV000235188.12

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1217C>T (p.Thr406Met)]

NM_001048174.2(MUTYH):c.1217C>T (p.Thr406Met)

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.1217C>T (p.Thr406Met)

Other names:

p.T434M:ACG>ATG

HGVS:

NC_000001.11:g.45331442G>A
NG_008189.1:g.14029C>T
NM_001048171.2:c.1217C>T
NM_001048172.2:c.1220C>T
NM_001048173.2:c.1217C>T
NM_001048174.2:c.1217C>TMANE SELECT
NM_001128425.2:c.1301C>T
NM_001293190.2:c.1262C>T
NM_001293191.2:c.1250C>T
NM_001293192.2:c.941C>T
NM_001293195.2:c.1217C>T
NM_001293196.2:c.941C>T
NM_001350650.2:c.872C>T
NM_001350651.2:c.872C>T
NM_012222.3:c.1292C>T
NP_001041636.1:p.Thr420Met
NP_001041636.2:p.Thr406Met
NP_001041637.1:p.Thr407Met
NP_001041638.1:p.Thr406Met
NP_001041639.1:p.Thr406Met
NP_001121897.1:p.Thr434Met
NP_001121897.1:p.Thr434Met
NP_001280119.1:p.Thr421Met
NP_001280120.1:p.Thr417Met
NP_001280121.1:p.Thr314Met
NP_001280124.1:p.Thr406Met
NP_001280125.1:p.Thr314Met
NP_001337579.1:p.Thr291Met
NP_001337580.1:p.Thr291Met
NP_036354.1:p.Thr431Met
LRG_220t1:c.1301C>T
LRG_220:g.14029C>T
LRG_220p1:p.Thr434Met
NC_000001.10:g.45797114G>A
NM_001048171.1:c.1259C>T
NM_001128425.1:c.1301C>T
NR_146882.2:n.1445C>T
NR_146883.2:n.1294C>T
p.T434M

Protein change:

T291M

Links:

dbSNP: rs587780084

NCBI 1000 Genomes Browser:

rs587780084

Molecular consequence:

NM_001048171.2:c.1217C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.1220C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.1217C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.1217C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.1301C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.1262C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.1250C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293192.2:c.941C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.1217C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293196.2:c.941C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350650.2:c.872C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350651.2:c.872C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.1292C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.1445C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1294C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000149666	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jun 4, 2023)	germline	clinical testing	Citation Link,
SCV000888306	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Dec 27, 2022)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25980754, 28135145, 33471991, 26467025
SCV002011065	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 3, 2021)	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

SCV000149666

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jun 4, 2023)

germline

clinical testing

Citation Link,

SCV000888306

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Dec 27, 2022)

unknown

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002011065

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 3, 2021)

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	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.

Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P, Roa BB, Wenstrup RJ, Hartman AR, Syngal S.

Gastroenterology. 2015 Sep;149(3):604-13.e20. doi: 10.1053/j.gastro.2015.05.006. Epub 2015 May 14.

PubMed [citation]

PMID:: 25980754
PMCID:: PMC4550537

Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

Yurgelun MB, Kulke MH, Fuchs CS, Allen BA, Uno H, Hornick JL, Ukaegbu CI, Brais LK, McNamara PG, Mayer RJ, Schrag D, Meyerhardt JA, Ng K, Kidd J, Singh N, Hartman AR, Wenstrup RJ, Syngal S.

J Clin Oncol. 2017 Apr 1;35(10):1086-1095. doi: 10.1200/JCO.2016.71.0012. Epub 2017 Jan 30.

PubMed [citation]

PMID:: 28135145
PMCID:: PMC5455355

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000149666.17

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

Description

In silico analysis supports that this missense variant does not alter protein structure/function; Also known as c.1259C>T, p.(Thr420Met); This variant is associated with the following publications: (PMID: 25980754, 28135145, 24728327, 23108399)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000888306.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The frequency of this variant in the general population, 0.000046 (6/129092 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with colorectal cancer (PMID: 28135145 (2017)) and an individual with a Lynch syndrome associated cancer (PMID: 25980754 (2015)). In a large-scale breast cancer association study, the variant was observed in individuals with breast cancer as well as in unaffected individuals (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/MUTYH)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

#	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

From Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV002011065.3

#	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	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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