NM_001128425.2(MUTYH):c.17C>A (p.Ser6Tyr) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 6, 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:: RCV000212695.17

Allele description [Variation Report for NM_001128425.2(MUTYH):c.17C>A (p.Ser6Tyr)]

NM_001128425.2(MUTYH):c.17C>A (p.Ser6Tyr)

Genes:

MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
TOE1:target of EGR1, exonuclease [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p34.1

Genomic location:

Preferred name:

NM_001128425.2(MUTYH):c.17C>A (p.Ser6Tyr)

Other names:

p.S6Y:TCC>TAC

HGVS:

NC_000001.11:g.45340238G>T
NG_008189.1:g.5233C>A
NG_090899.1:g.847G>T
NG_090900.1:g.179G>T
NM_001048171.2:c.-26C>A
NM_001128425.2:c.17C>A
NM_001293190.2:c.17C>A
NM_001293192.2:c.-238C>A
NM_001350650.2:c.-297C>A
NM_001350651.2:c.-233C>A
NM_001407069.1:c.17C>A
NM_001407070.1:c.-42C>A
NM_001407071.1:c.-42C>A
NM_001407072.1:c.-22C>A
NM_001407073.1:c.17C>A
NM_012222.3:c.17C>A
NM_025077.4:c.-15G>TMANE SELECT
NP_001121897.1:p.Ser6Tyr
NP_001121897.1:p.Ser6Tyr
NP_001280119.1:p.Ser6Tyr
NP_001393998.1:p.Ser6Tyr
NP_001394002.1:p.Ser6Tyr
NP_036354.1:p.Ser6Tyr
LRG_220t1:c.17C>A
LRG_220:g.5233C>A
LRG_220p1:p.Ser6Tyr
NC_000001.10:g.45805910G>T
NM_001048171.1:c.17C>A
NM_001128425.1:c.17C>A
NR_146882.2:n.203C>A
NR_176269.1:n.203C>A
NR_176274.1:n.203C>A
p.S6Y

Protein change:

S6Y

Links:

dbSNP: rs587782837

NCBI 1000 Genomes Browser:

rs587782837

Molecular consequence:

NM_001048171.2:c.-26C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001293192.2:c.-238C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350650.2:c.-297C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350651.2:c.-233C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001407070.1:c.-42C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001407071.1:c.-42C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001407072.1:c.-22C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_025077.4:c.-15G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001128425.2:c.17C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.17C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407069.1:c.17C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407073.1:c.17C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.17C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.203C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176269.1:n.203C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176274.1:n.203C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000691954	Mayo Clinic Laboratories, Mayo Clinic	no assertion criteria provided	Uncertain significance	unknown	clinical testing
SCV000919798	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Nov 6, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25186627, 27720647 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000691954

Mayo Clinic Laboratories, Mayo Clinic

no assertion criteria provided

Uncertain significance

unknown

clinical testing

SCV000919798

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Nov 6, 2023)

germline

clinical testing

PubMed (2)
[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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel.

Tung N, Battelli C, Allen B, Kaldate R, Bhatnagar S, Bowles K, Timms K, Garber JE, Herold C, Ellisen L, Krejdovsky J, DeLeonardis K, Sedgwick K, Soltis K, Roa B, Wenstrup RJ, Hartman AR.

Cancer. 2015 Jan 1;121(1):25-33. doi: 10.1002/cncr.29010. Epub 2014 Sep 3.

PubMed [citation]

PMID:: 25186627

Sanger Confirmation Is Required to Achieve Optimal Sensitivity and Specificity in Next-Generation Sequencing Panel Testing.

Mu W, Lu HM, Chen J, Li S, Elliott AM.

J Mol Diagn. 2016 Nov;18(6):923-932. doi: 10.1016/j.jmoldx.2016.07.006. Epub 2016 Oct 6.

PubMed [citation]

PMID:: 27720647

Details of each submission

From Mayo Clinic Laboratories, Mayo Clinic, SCV000691954.1

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

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919798.2

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

Description

Variant summary: MUTYH c.17C>A (p.Ser6Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 9.6e-05 in 249362 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in MUTYH causing Hereditary Breast And Ovarian Cancer Syndrome (9.6e-05 vs 0.0056), allowing no conclusion about variant significance. c.17C>A has been reported in the literature in individuals affected with MUTYH-associated Polyposis (Tung_2014) or unspecified individual(s) undertaking cancel panel testing (Mu_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome or other MUTYH-related diseases. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 27720647, 25186627). Eight submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified 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: Sep 29, 2024

ClinVar

Relating variation to medicine