NM_001048174.2(MUTYH):c.1130C>T (p.Pro377Leu) AND Carcinoma of colon

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 24, 2014
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000144633.11

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1130C>T (p.Pro377Leu)]

NM_001048174.2(MUTYH):c.1130C>T (p.Pro377Leu)

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.1130C>T (p.Pro377Leu)

HGVS:

NC_000001.11:g.45331529G>A
NG_008189.1:g.13942C>T
NM_001048171.2:c.1130C>T
NM_001048172.2:c.1133C>T
NM_001048173.2:c.1130C>T
NM_001048174.2:c.1130C>TMANE SELECT
NM_001128425.2:c.1214C>T
NM_001293190.2:c.1175C>T
NM_001293191.2:c.1163C>T
NM_001293192.2:c.854C>T
NM_001293195.2:c.1130C>T
NM_001293196.2:c.854C>T
NM_001350650.2:c.785C>T
NM_001350651.2:c.785C>T
NM_012222.3:c.1205C>T
NP_001041636.1:p.Pro391Leu
NP_001041636.2:p.Pro377Leu
NP_001041637.1:p.Pro378Leu
NP_001041638.1:p.Pro377Leu
NP_001041639.1:p.Pro377Leu
NP_001121897.1:p.Pro405Leu
NP_001121897.1:p.Pro405Leu
NP_001280119.1:p.Pro392Leu
NP_001280120.1:p.Pro388Leu
NP_001280121.1:p.Pro285Leu
NP_001280124.1:p.Pro377Leu
NP_001280125.1:p.Pro285Leu
NP_001337579.1:p.Pro262Leu
NP_001337580.1:p.Pro262Leu
NP_036354.1:p.Pro402Leu
NP_036354.1:p.Pro402Leu
LRG_220t1:c.1214C>T
LRG_220:g.13942C>T
LRG_220p1:p.Pro405Leu
NC_000001.10:g.45797201G>A
NM_001048171.1:c.1172C>T
NM_001128425.1:c.1214C>T
NM_012222.2:c.1205C>T
NR_146882.2:n.1358C>T
NR_146883.2:n.1207C>T
p.P405L

Protein change:

P262L

Links:

dbSNP: rs529008617

NCBI 1000 Genomes Browser:

rs529008617

Molecular consequence:

NM_001048171.2:c.1130C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.1133C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.1130C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.1130C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.1214C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.1175C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.1163C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293192.2:c.854C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.1130C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293196.2:c.854C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350650.2:c.785C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350651.2:c.785C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.1205C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.1358C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1207C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Carcinoma of colon (CRC)
Synonyms:: Colonic carcinoma; Colon carcinoma
Identifiers:: MONDO: MONDO:0002032; MedGen: C0699790

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000189960	Pathway Genomics	no assertion criteria provided	Pathogenic (Jul 24, 2014)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16140997, 19732775, 19836313, 20848659
SCV000592712	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Pathogenic	unknown	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000189960

Pathway Genomics

no assertion criteria provided

Pathogenic
(Jul 24, 2014)

germline

clinical testing

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

SCV000592712

Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided

Pathogenic

unknown

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	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

Multiplicity in polyp count and extracolonic manifestations in 40 Dutch patients with MYH associated polyposis coli (MAP).

Nielsen M, Franken PF, Reinards TH, Weiss MM, Wagner A, van der Klift H, Kloosterman S, Houwing-Duistermaat JJ, Aalfs CM, Ausems MG, Bröcker-Vriends AH, Gomez Garcia EB, Hoogerbrugge N, Menko FH, Sijmons RH, Verhoef S, Kuipers EJ, Morreau H, Breuning MH, Tops CM, Wijnen JT, Vasen HF, et al.

J Med Genet. 2005 Sep;42(9):e54.

PubMed [citation]

PMID:: 16140997
PMCID:: PMC1736132

Expanded extracolonic tumor spectrum in MUTYH-associated polyposis.

Vogt S, Jones N, Christian D, Engel C, Nielsen M, Kaufmann A, Steinke V, Vasen HF, Propping P, Sampson JR, Hes FJ, Aretz S.

Gastroenterology. 2009 Dec;137(6):1976-85.e1-10. doi: 10.1053/j.gastro.2009.08.052. Epub 2009 Sep 2.

PubMed [citation]

PMID:: 19732775

See all PubMed Citations (4)

Details of each submission

From Pathway Genomics, SCV000189960.1

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

#	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 Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000592712.2

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

Description

The p.Pro405Leu (Alias: p.Pro391Leu) variant has been previously reported in the literature in 30/1730 proband chromosomes, of whom 23 were homozygous or compound heterozygous for this variant or a second pathogenic variant, consistent with the autosomal recessive inheritance of the MUTYH-associated polyposis coli. The variant was not observed in 424 controls (Aretz 2006, Bouquen 2007, Goto_2010, Kanter-Smoler 2006, Kundu 2009, Middeldorp 2008, Nielsen 2005, Vogt 2009). The MYH Pro405/391 residue is conserved across mammals, and computational analyses (PolyPhen, SIFT, AlignGVGD) suggest that the variant may impact the protein. Although this information is not predictive enough to assume pathogenicity, functional studies analyzing the adenine glycosylase activity have shown that the variant showed compromised enzymatic activity that was 30â€šÃ„Ã¬40% of the wild type enzyme. (Goto 2010, Kundu 2009). In summary, based on the above information, this variant is classified as pathogenic.

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

Last Updated: Jan 19, 2025

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