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NM_001048174.2(MUTYH):c.954G>A (p.Ser318=)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(4);Uncertain significance(4)

Review status:
criteria provided, conflicting interpretations
Submissions:
9 (Most recent: Sep 29, 2021)
Last evaluated:
Feb 1, 2021
Accession:
VCV000186251.21
Variation ID:
186251
Description:
single nucleotide variant
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NM_001048174.2(MUTYH):c.954G>A (p.Ser318=)

Allele ID
181675
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1p34.1
Genomic location
1: 45331809 (GRCh38) GRCh38 UCSC
1: 45797481 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.10:g.45797481C>T
NM_001128425.1:c.1038G>A NP_001121897.1:p.Ser346= synonymous
NM_012222.2:c.1029G>A NP_036354.1:p.Ser343= synonymous
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000001.11:45331808:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00007
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Links
ClinGen: CA012034
dbSNP: rs372673338
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Mar 29, 2016 RCV000255834.2
Uncertain significance 2 criteria provided, single submitter Oct 15, 2020 RCV000459930.8
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Jan 12, 2021 RCV000165812.8
Conflicting interpretations of pathogenicity 4 criteria provided, conflicting interpretations Feb 1, 2021 RCV000584863.7
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
MUTYH - - GRCh38
GRCh37
1650 1755

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Oct 13, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000216559.5
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (4)
Comment:
The c.1038G>A variant (also known as p.S346S), located in coding exon 12 of the MUTYH gene, results from a G to A substitution at nucleotide … (more)
Uncertain significance
(Mar 29, 2016)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000539817.1
Submitted: (Apr 03, 2017)
Evidence details
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Uncertain significance
(Jan 09, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000889517.2
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (4)
Likely pathogenic
(Feb 01, 2021)
criteria provided, single submitter
Method: clinical testing
not provided
(Autosomal recessive inheritance)
Allele origin: germline
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001480054.1
Submitted: (Feb 01, 2021)
Evidence details
Uncertain significance
(Oct 15, 2020)
criteria provided, single submitter
Method: clinical testing
MYH-associated polyposis
Allele origin: germline
Invitae
Accession: SCV000545703.7
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (6)
Comment:
This sequence change affects codon 346 of the MUTYH mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid … (more)
Uncertain significance
(Jan 12, 2021)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000685535.4
Submitted: (Jun 11, 2021)
Evidence details
Comment:
This variant is a synonymous variant located in exon 12 of the MUTYH gene. This variant is also known as c.996G>A (p.Ser332=) in the literature … (more)
Likely pathogenic
(Mar 26, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000321910.9
Submitted: (Sep 29, 2021)
Evidence details
Comment:
Splice variant demonstrated to result in the creation of novel splice acceptor site which may result in the deletion of 14 amino acids of exon … (more)
Likely pathogenic
(Aug 01, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV000692628.10
Submitted: (Jul 04, 2021)
Evidence details
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
MYH-associated polyposis
Allele origin: germline
Genomics England Pilot Project,Genomics England
Accession: SCV001760034.1
Submitted: (Jul 15, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Base excision repair deficiency signatures implicate germline and somatic <i>MUTYH</i> aberrations in pancreatic ductal adenocarcinoma and breast cancer oncogenesis. Thibodeau ML Cold Spring Harbor molecular case studies 2019 PMID: 30833417
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. Xiong HY Science (New York, N.Y.) 2015 PMID: 25525159
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 Cancer 2015 PMID: 25186627
LOVD v.2.0: the next generation in gene variant databases. Fokkema IF Human mutation 2011 PMID: 21520333
Similar colorectal cancer risk in patients with monoallelic and biallelic mutations in the MYH gene identified in a population with adenomatous polyposis. Olschwang S Genetic testing 2007 PMID: 17949294
Mutation analysis of the MYH gene in an Australian series of colorectal polyposis patients with or without germline APC mutations. Kairupan CF International journal of cancer 2005 PMID: 15761860

Text-mined citations for rs372673338...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 30, 2021