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NM_001048174.2(MUTYH):c.461G>C (p.Arg154Pro) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 14, 2023
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:
RCV001024139.12

Allele description [Variation Report for NM_001048174.2(MUTYH):c.461G>C (p.Arg154Pro)]

NM_001048174.2(MUTYH):c.461G>C (p.Arg154Pro)

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.461G>C (p.Arg154Pro)
HGVS:
  • NC_000001.11:g.45332794C>G
  • NG_008189.1:g.12677G>C
  • NM_001048171.2:c.461G>C
  • NM_001048172.2:c.464G>C
  • NM_001048173.2:c.461G>C
  • NM_001048174.2:c.461G>CMANE SELECT
  • NM_001128425.2:c.545G>C
  • NM_001293190.2:c.506G>C
  • NM_001293191.2:c.494G>C
  • NM_001293192.2:c.185G>C
  • NM_001293195.2:c.461G>C
  • NM_001293196.2:c.185G>C
  • NM_001350650.2:c.116G>C
  • NM_001350651.2:c.116G>C
  • NM_012222.3:c.536G>C
  • NP_001041636.2:p.Arg154Pro
  • NP_001041637.1:p.Arg155Pro
  • NP_001041638.1:p.Arg154Pro
  • NP_001041639.1:p.Arg154Pro
  • NP_001121897.1:p.Arg182Pro
  • NP_001121897.1:p.Arg182Pro
  • NP_001280119.1:p.Arg169Pro
  • NP_001280120.1:p.Arg165Pro
  • NP_001280121.1:p.Arg62Pro
  • NP_001280124.1:p.Arg154Pro
  • NP_001280125.1:p.Arg62Pro
  • NP_001337579.1:p.Arg39Pro
  • NP_001337580.1:p.Arg39Pro
  • NP_036354.1:p.Arg179Pro
  • LRG_220t1:c.545G>C
  • LRG_220:g.12677G>C
  • LRG_220p1:p.Arg182Pro
  • NC_000001.10:g.45798466C>G
  • NM_001128425.1:c.545G>C
  • NR_146882.2:n.689G>C
  • NR_146883.2:n.538G>C
Protein change:
R154P
Links:
dbSNP: rs143353451
NCBI 1000 Genomes Browser:
rs143353451
Molecular consequence:
  • NM_001048171.2:c.461G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.2:c.464G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.2:c.461G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.2:c.461G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.2:c.545G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.2:c.506G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.2:c.494G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293192.2:c.185G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.2:c.461G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293196.2:c.185G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350650.2:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350651.2:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.3:c.536G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.2:n.689G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.2:n.538G>C - 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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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001186106Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Jun 14, 2023) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Ambry Genetics, SCV001186106.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.R182P variant (also known as c.545G>C), located in coding exon 7 of the MUTYH gene, results from a G to C substitution at nucleotide position 545. The arginine at codon 182 is replaced by proline, an amino acid with dissimilar properties. Based on internal structural analysis, this variant is more disruptive than known pathogenic variants (Ambry internal data). A different alteration at this position, p.R182H, has been identified in trans in several individuals with MAP phenotypes and has been determined to be functionally deficient (Isidro et al. Hum Mutat 2004 Oct; 24(4):353-4; Di Gregorio et al. Gastroenterology 2006 Aug; 131(2):439-44; Aretz et al. Int J Cancer 2006 Aug 15;119(4): 807-14; Jones N et al. Gastroenterology. 2009 Aug;137(2):489-94, 494.e1; Morak M et al. Clin Genet. 2010 Oct;78(4):353-63; Goto et al. Hum Mutat 2010 Nov; 31(11):E1861-74; Komine K et al. Hum. Mutat., 2015 Jul;36:704-11). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 8, 2024