NM_001048174.2(MUTYH):c.1463C>T (p.Pro488Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Sep 20, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV000131522.13

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1463C>T (p.Pro488Leu)]

NM_001048174.2(MUTYH):c.1463C>T (p.Pro488Leu)

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.1463C>T (p.Pro488Leu)

HGVS:

NC_000001.11:g.45329409G>A
NG_008189.1:g.16062C>T
NM_001048171.2:c.1463C>T
NM_001048172.2:c.1466C>T
NM_001048173.2:c.1463C>T
NM_001048174.2:c.1463C>TMANE SELECT
NM_001128425.2:c.1547C>T
NM_001293190.2:c.1508C>T
NM_001293191.2:c.1496C>T
NM_001293192.2:c.1187C>T
NM_001293195.2:c.1463C>T
NM_001293196.2:c.1187C>T
NM_001350650.2:c.1118C>T
NM_001350651.2:c.1118C>T
NM_012222.3:c.1538C>T
NP_001041636.2:p.Pro488Leu
NP_001041637.1:p.Pro489Leu
NP_001041638.1:p.Pro488Leu
NP_001041639.1:p.Pro488Leu
NP_001121897.1:p.Pro516Leu
NP_001121897.1:p.Pro516Leu
NP_001280119.1:p.Pro503Leu
NP_001280120.1:p.Pro499Leu
NP_001280121.1:p.Pro396Leu
NP_001280124.1:p.Pro488Leu
NP_001280125.1:p.Pro396Leu
NP_001337579.1:p.Pro373Leu
NP_001337580.1:p.Pro373Leu
NP_036354.1:p.Pro513Leu
LRG_220t1:c.1547C>T
LRG_220:g.16062C>T
LRG_220p1:p.Pro516Leu
NC_000001.10:g.45795081G>A
NM_001128425.1:c.1547C>T
NR_146882.2:n.1871C>T
NR_146883.2:n.1720C>T
p.P516L

Protein change:

P373L

Links:

dbSNP: rs587778542

NCBI 1000 Genomes Browser:

rs587778542

Molecular consequence:

NM_001048171.2:c.1463C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.1466C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.1463C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.1463C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.1547C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.1508C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.1496C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293192.2:c.1187C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.1463C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293196.2:c.1187C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350650.2:c.1118C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350651.2:c.1118C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.1538C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.1871C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1720C>T - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000186516	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (May 2, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20618354, 25820570, 26377631 Citation Link,
SCV000903067	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Mar 14, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002532253	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Sep 20, 2021)	germline	curation	PubMed (6) [See all records that cite these PMIDs] 33471991, 20618354, 14991577, 14579148, 26377631, 25820570 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000186516

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(May 2, 2019)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV000903067

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Mar 14, 2017)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002532253

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Sep 20, 2021)

germline

curation

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

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, curation

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Breast Cancer Association Consortium., Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q, Bolla MK, Dennis J, Keeman R, Alonso MR, Álvarez N, Herraez B, Fernandez V, Núñez-Torres R, Osorio A, Valcich J, Li M, et al.

N Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948. Epub 2021 Jan 20.

PubMed [citation]

PMID:: 33471991
PMCID:: PMC7611105

See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV000186516.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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 Color Diagnostics, LLC DBA Color Health, SCV000903067.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Sema4, Sema4, SCV002532253.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (6)

#	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: May 7, 2024

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