NM_001048174.2(MUTYH):c.1417C>T (p.Gln473Ter) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 21, 2018
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:: RCV000760568.2

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1417C>T (p.Gln473Ter)]

NM_001048174.2(MUTYH):c.1417C>T (p.Gln473Ter)

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.1417C>T (p.Gln473Ter)

HGVS:

NC_000001.11:g.45330533G>A
NG_008189.1:g.14938C>T
NM_001048171.2:c.1417C>T
NM_001048172.2:c.1420C>T
NM_001048173.2:c.1417C>T
NM_001048174.2:c.1417C>TMANE SELECT
NM_001128425.2:c.1501C>T
NM_001293190.2:c.1462C>T
NM_001293191.2:c.1450C>T
NM_001293192.2:c.1141C>T
NM_001293195.2:c.1417C>T
NM_001293196.2:c.1141C>T
NM_001350650.2:c.1072C>T
NM_001350651.2:c.1072C>T
NM_012222.3:c.1492C>T
NP_001041636.2:p.Gln473Ter
NP_001041637.1:p.Gln474Ter
NP_001041638.1:p.Gln473Ter
NP_001041639.1:p.Gln473Ter
NP_001121897.1:p.Gln501Ter
NP_001121897.1:p.Gln501Ter
NP_001280119.1:p.Gln488Ter
NP_001280120.1:p.Gln484Ter
NP_001280121.1:p.Gln381Ter
NP_001280124.1:p.Gln473Ter
NP_001280125.1:p.Gln381Ter
NP_001337579.1:p.Gln358Ter
NP_001337580.1:p.Gln358Ter
NP_036354.1:p.Gln498Ter
LRG_220t1:c.1501C>T
LRG_220:g.14938C>T
LRG_220p1:p.Gln501Ter
NC_000001.10:g.45796205G>A
NM_001128425.1:c.1501C>T
NR_146882.2:n.1645C>T
NR_146883.2:n.1494C>T

Protein change:

Q358*

Links:

dbSNP: rs932830392

NCBI 1000 Genomes Browser:

rs932830392

Molecular consequence:

NR_146882.2:n.1645C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1494C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001048171.2:c.1417C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001048172.2:c.1420C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001048173.2:c.1417C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001048174.2:c.1417C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001128425.2:c.1501C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293190.2:c.1462C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293191.2:c.1450C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293192.2:c.1141C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293195.2:c.1417C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293196.2:c.1141C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001350650.2:c.1072C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001350651.2:c.1072C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_012222.3:c.1492C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000890459	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (May 21, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000890459

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(May 21, 2018)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000890459.1

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

Description

This variant is denoted MUTYH c.1501C>T at the cDNA level and p.Gln501Ter (Q501X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through protein truncation. Even though this frameshift occurs near the end of the gene in the second to last exon, and nonsense-mediated decay is not expected to occur, it is significant since the last 49 amino acids are no longer translated. Furthermore, the truncation would disrupt the PCNA domain (Parker 2001, Ruggieri 2013). Although this variant has not, to our knowledge, been reported in the literature as a germline variant, it is considered likely pathogenic.

#	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

Last Updated: Apr 7, 2025

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