NM_001048174.2(MUTYH):c.1174C>G (p.Leu392Val) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 16, 2020
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:: RCV001201302.1

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1174C>G (p.Leu392Val)]

NM_001048174.2(MUTYH):c.1174C>G (p.Leu392Val)

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.1174C>G (p.Leu392Val)

HGVS:

NC_000001.11:g.45331485G>C
NG_008189.1:g.13986C>G
NM_001048171.2:c.1174C>G
NM_001048172.2:c.1177C>G
NM_001048173.2:c.1174C>G
NM_001048174.2:c.1174C>GMANE SELECT
NM_001128425.2:c.1258C>G
NM_001293190.2:c.1219C>G
NM_001293191.2:c.1207C>G
NM_001293192.2:c.898C>G
NM_001293195.2:c.1174C>G
NM_001293196.2:c.898C>G
NM_001350650.2:c.829C>G
NM_001350651.2:c.829C>G
NM_012222.3:c.1249C>G
NP_001041636.1:p.Leu406Val
NP_001041636.2:p.Leu392Val
NP_001041637.1:p.Leu393Val
NP_001041638.1:p.Leu392Val
NP_001041639.1:p.Leu392Val
NP_001121897.1:p.Leu420Val
NP_001121897.1:p.Leu420Val
NP_001280119.1:p.Leu407Val
NP_001280120.1:p.Leu403Val
NP_001280121.1:p.Leu300Val
NP_001280124.1:p.Leu392Val
NP_001280125.1:p.Leu300Val
NP_001337579.1:p.Leu277Val
NP_001337580.1:p.Leu277Val
NP_036354.1:p.Leu417Val
LRG_220t1:c.1258C>G
LRG_220:g.13986C>G
LRG_220p1:p.Leu420Val
NC_000001.10:g.45797157G>C
NM_001048171.1:c.1216C>G
NM_001128425.1:c.1258C>G
NR_146882.2:n.1402C>G
NR_146883.2:n.1251C>G

Protein change:

L277V

Links:

dbSNP: rs144079536

NCBI 1000 Genomes Browser:

rs144079536

Molecular consequence:

NM_001048171.2:c.1174C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.1177C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.1174C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.1174C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.1258C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.1219C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.1207C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001293192.2:c.898C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.1174C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001293196.2:c.898C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001350650.2:c.829C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001350651.2:c.829C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.1249C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.1402C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1251C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001372439	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jun 16, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001372439

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jun 16, 2020)

germline

clinical testing

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

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

Citations

PubMed

Next-generation sequencing in familial breast cancer patients from Lebanon.

Jalkh N, Chouery E, Haidar Z, Khater C, Atallah D, Ali H, Marafie MJ, Al-Mulla MR, Al-Mulla F, Megarbane A.

BMC Med Genomics. 2017 Feb 15;10(1):8. doi: 10.1186/s12920-017-0244-7.

PubMed [citation]

PMID:: 28202063
PMCID:: PMC5312584

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001372439.1

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

Description

Variant summary: MUTYH c.1258C>G (p.Leu420Val) results in a conservative amino acid change located in the NUDIX hydrolase domain (IPR000086) / MutY, C-terminal (IPR029119) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251166 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1258C>G has been reported in the literature in individuals affected with breast cancer (Jalkh_2017). This report, however does not provide unequivocal conclusions about association of the variant with MUTYH-Associated Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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: Apr 7, 2025

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