NM_001048174.2(MUTYH):c.1112_1119del (p.Ala371fs) AND Familial adenomatous polyposis 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 22, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002898965.2

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1112_1119del (p.Ala371fs)]

NM_001048174.2(MUTYH):c.1112_1119del (p.Ala371fs)

Gene:

MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p34.1

Genomic location:

Preferred name:

NM_001048174.2(MUTYH):c.1112_1119del (p.Ala371fs)

HGVS:

NC_000001.11:g.45331541_45331548del
NG_008189.1:g.13924_13931del
NM_001048171.2:c.1112_1119del
NM_001048172.2:c.1115_1122del
NM_001048173.2:c.1112_1119del
NM_001048174.2:c.1112_1119delMANE SELECT
NM_001128425.2:c.1196_1203del
NM_001293190.2:c.1157_1164del
NM_001293191.2:c.1145_1152del
NM_001293192.2:c.836_843del
NM_001293195.2:c.1112_1119del
NM_001293196.2:c.836_843del
NM_001350650.2:c.767_774del
NM_001350651.2:c.767_774del
NM_001407069.1:c.1144_1151delGCAGGACT
NM_001407070.1:c.1111_1118delGCAGGACT
NM_001407071.1:c.1114_1121delGCAGGACT
NM_001407072.1:c.1111_1118delGCAGGACT
NM_001407073.1:c.1111_1118delGCAGGACT
NM_001407075.1:c.1027_1034delGCAGGACT
NM_001407077.1:c.1144_1151delGCAGGACT
NM_001407078.1:c.1114_1121delGCAGGACT
NM_001407079.1:c.1072_1079delGCAGGACT
NM_001407080.1:c.1069_1076delGCAGGACT
NM_001407081.1:c.1111_1118delGCAGGACT
NM_001407082.1:c.766_773delGCAGGACT
NM_001407083.1:c.1153_1160delGCAGGACT
NM_001407085.1:c.1153_1160delGCAGGACT
NM_001407086.1:c.1114_1121delGCAGGACT
NM_001407087.1:c.1132_1139delGCAGGACT
NM_001407088.1:c.1111_1118delGCAGGACT
NM_001407089.1:c.1111_1118delGCAGGACT
NM_001407091.1:c.835_842delGCAGGACT
NM_012222.3:c.1187_1194del
NP_001041636.2:p.Ala371fs
NP_001041637.1:p.Ala372fs
NP_001041638.1:p.Ala371fs
NP_001041639.1:p.Ala371fs
NP_001121897.1:p.Ala399Valfs
NP_001121897.1:p.Ala399fs
NP_001280119.1:p.Ala386fs
NP_001280120.1:p.Ala382fs
NP_001280121.1:p.Ala279fs
NP_001280124.1:p.Ala371fs
NP_001280125.1:p.Ala279fs
NP_001337579.1:p.Ala256fs
NP_001337580.1:p.Ala256fs
NP_001393998.1:p.Ala382Valfs
NP_001393999.1:p.Ala371Valfs
NP_001394000.1:p.Ala372Valfs
NP_001394001.1:p.Ala371Valfs
NP_001394002.1:p.Ala371Valfs
NP_001394004.1:p.Ala343Valfs
NP_001394006.1:p.Ala382Valfs
NP_001394007.1:p.Ala372Valfs
NP_001394008.1:p.Ala358Valfs
NP_001394009.1:p.Ala357Valfs
NP_001394010.1:p.Ala371Valfs
NP_001394011.1:p.Ala256Valfs
NP_001394012.1:p.Ala385Valfs
NP_001394014.1:p.Ala385Valfs
NP_001394015.1:p.Ala372Valfs
NP_001394016.1:p.Ala378Valfs
NP_001394017.1:p.Ala371Valfs
NP_001394018.1:p.Ala371Valfs
NP_001394020.1:p.Ala279Valfs
NP_036354.1:p.Ala396fs
LRG_220t1:c.1195_1202del
LRG_220:g.13924_13931del
LRG_220p1:p.Ala399Valfs
NC_000001.10:g.45797212_45797219del
NC_000001.10:g.45797213_45797220del
NM_001128425.1:c.1195_1202delGCAGGACT
NR_146882.2:n.1340_1347del
NR_146883.2:n.1189_1196del
NR_176269.1:n.1335_1342delGCAGGACT
NR_176270.1:n.1275_1282delGCAGGACT
NR_176271.1:n.1198_1205delGCAGGACT
NR_176272.1:n.1262_1269delGCAGGACT
NR_176273.1:n.1220_1227delGCAGGACT
NR_176274.1:n.1275_1282delGCAGGACT

Protein change:

A256fs

Molecular consequence:

NM_001048171.2:c.1112_1119del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001048172.2:c.1115_1122del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001048173.2:c.1112_1119del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001048174.2:c.1112_1119del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001128425.2:c.1196_1203del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001293190.2:c.1157_1164del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001293191.2:c.1145_1152del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001293192.2:c.836_843del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001293195.2:c.1112_1119del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001293196.2:c.836_843del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001350650.2:c.767_774del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001350651.2:c.767_774del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407069.1:c.1144_1151delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407070.1:c.1111_1118delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407071.1:c.1114_1121delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407072.1:c.1111_1118delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407073.1:c.1111_1118delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407075.1:c.1027_1034delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407077.1:c.1144_1151delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407078.1:c.1114_1121delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407079.1:c.1072_1079delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407080.1:c.1069_1076delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407081.1:c.1111_1118delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407082.1:c.766_773delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407083.1:c.1153_1160delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407085.1:c.1153_1160delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407086.1:c.1114_1121delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407087.1:c.1132_1139delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407088.1:c.1111_1118delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407089.1:c.1111_1118delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407091.1:c.835_842delGCAGGACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_012222.3:c.1187_1194del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_146882.2:n.1340_1347del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1189_1196del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Familial adenomatous polyposis 2
Synonyms:: COLORECTAL ADENOMATOUS POLYPOSIS, AUTOSOMAL RECESSIVE; ADENOMAS, MULTIPLE COLORECTAL, AUTOSOMAL RECESSIVE; MYH-associated polyposis; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012041; MedGen: C3272841; Orphanet: 220460; OMIM: 608456

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003238668	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 22, 2022)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 16140997, 16557584, 16616356, 17161978, 19732775, 19836313, 20191381, 20848659, 23322991, 25820570, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003238668

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 22, 2022)

germline

clinical testing

PubMed (11)
[See all records that cite these PMIDs]

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

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

MUTYH-associated polyposis: 70 of 71 patients with biallelic mutations present with an attenuated or atypical phenotype.

Aretz S, Uhlhaas S, Goergens H, Siberg K, Vogel M, Pagenstecher C, Mangold E, Caspari R, Propping P, Friedl W.

Int J Cancer. 2006 Aug 15;119(4):807-14.

PubMed [citation]

PMID:: 16557584

See all PubMed Citations (11)

Details of each submission

From Invitae, SCV003238668.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MUTYH protein in which other variant(s) (p.Pro405Leu) have been determined to be pathogenic (PMID: 16140997, 16557584, 16616356, 17161978, 19732775, 19836313, 20191381, 20848659, 23322991, 25820570). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala399Valfs*130) in the MUTYH gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 151 amino acid(s) of the MUTYH protein.

#	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: Feb 20, 2024

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