NM_001048174.2(MUTYH):c.1512C>A (p.Phe504Leu) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 11, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001582750.12

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1512C>A (p.Phe504Leu)]

NM_001048174.2(MUTYH):c.1512C>A (p.Phe504Leu)

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.1512C>A (p.Phe504Leu)

HGVS:

NC_000001.11:g.45329360G>T
NG_008189.1:g.16111C>A
NM_001048171.2:c.1512C>A
NM_001048172.2:c.1515C>A
NM_001048173.2:c.1512C>A
NM_001048174.2:c.1512C>AMANE SELECT
NM_001128425.2:c.1596C>A
NM_001293190.2:c.1557C>A
NM_001293191.2:c.1545C>A
NM_001293192.2:c.1236C>A
NM_001293195.2:c.1512C>A
NM_001293196.2:c.1236C>A
NM_001350650.2:c.1167C>A
NM_001350651.2:c.1167C>A
NM_012222.3:c.1587C>A
NP_001041636.2:p.Phe504Leu
NP_001041637.1:p.Phe505Leu
NP_001041638.1:p.Phe504Leu
NP_001041639.1:p.Phe504Leu
NP_001121897.1:p.Phe532Leu
NP_001121897.1:p.Phe532Leu
NP_001280119.1:p.Phe519Leu
NP_001280120.1:p.Phe515Leu
NP_001280121.1:p.Phe412Leu
NP_001280124.1:p.Phe504Leu
NP_001280125.1:p.Phe412Leu
NP_001337579.1:p.Phe389Leu
NP_001337580.1:p.Phe389Leu
NP_036354.1:p.Phe529Leu
LRG_220t1:c.1596C>A
LRG_220:g.16111C>A
LRG_220p1:p.Phe532Leu
NC_000001.10:g.45795032G>T
NM_001128425.1:c.1596C>A
NR_146882.2:n.1920C>A
NR_146883.2:n.1769C>A

Protein change:

F389L

Links:

dbSNP: rs768671057

NCBI 1000 Genomes Browser:

rs768671057

Molecular consequence:

NM_001048171.2:c.1512C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.1515C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.1512C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.1512C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.1596C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.1557C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.1545C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293192.2:c.1236C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.1512C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293196.2:c.1236C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350650.2:c.1167C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350651.2:c.1167C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.1587C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.1920C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1769C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000601641	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jan 11, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 35668106, 26467025
SCV001819647	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Feb 25, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000601641

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Jan 11, 2023)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001819647

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Feb 25, 2020)

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identifying colorectal cancer caused by biallelic MUTYH pathogenic variants using tumor mutational signatures.

Georgeson P, Harrison TA, Pope BJ, Zaidi SH, Qu C, Steinfelder RS, Lin Y, Joo JE, Mahmood K, Clendenning M, Walker R, Amitay EL, Berndt SI, Brenner H, Campbell PT, Cao Y, Chan AT, Chang-Claude J, Doheny KF, Drew DA, Figueiredo JC, French AJ, et al.

Nat Commun. 2022 Jun 6;13(1):3254. doi: 10.1038/s41467-022-30916-1.

PubMed [citation]

PMID:: 35668106
PMCID:: PMC9170691

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000601641.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The frequency of this variant in the general population, 0.00023 (8/35440 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported as a somatic variant in an individual with colorectal cancer (PMID: 35668106 (2022)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

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

From GeneDx, SCV001819647.1

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

Description

In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

#	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: Nov 10, 2024

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