ClinVar Genomic variation as it relates to human health
NM_001128425.2(MUTYH):c.17C>A (p.Ser6Tyr)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(8); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001128425.2(MUTYH):c.17C>A (p.Ser6Tyr)
Variation ID: 142941 Accession: VCV000142941.35
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p34.1 1: 45340238 (GRCh38) [ NCBI UCSC ] 1: 45805910 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Feb 19, 2018 Oct 8, 2024 Apr 26, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_025077.4:c.-15G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
5 prime UTR NM_001128425.2:c.17C>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121897.1:p.Ser6Tyr missense NM_001048171.2:c.-26C>A 5 prime UTR NM_001293190.2:c.17C>A NP_001280119.1:p.Ser6Tyr missense NM_001293192.2:c.-238C>A 5 prime UTR NM_001350650.2:c.-297C>A 5 prime UTR NM_001350651.2:c.-233C>A 5 prime UTR NM_001407069.1:c.17C>A NP_001393998.1:p.Ser6Tyr missense NM_001407070.1:c.-42C>A 5 prime UTR NM_001407071.1:c.-42C>A 5 prime UTR NM_001407072.1:c.-22C>A 5 prime UTR NM_001407073.1:c.17C>A NP_001394002.1:p.Ser6Tyr missense NM_012222.3:c.17C>A NP_036354.1:p.Ser6Tyr missense NR_146882.2:n.203C>A non-coding transcript variant NR_176269.1:n.203C>A non-coding transcript variant NR_176274.1:n.203C>A non-coding transcript variant NC_000001.11:g.45340238G>T NC_000001.10:g.45805910G>T NG_008189.1:g.5233C>A NG_090899.1:g.847G>T NG_090900.1:g.179G>T LRG_220:g.5233C>A LRG_220t1:c.17C>A LRG_220p1:p.Ser6Tyr - Protein change
- S6Y
- Other names
- p.S6Y:TCC>TAC
- Canonical SPDI
- NC_000001.11:45340237:G:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00010
The Genome Aggregation Database (gnomAD) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00004
Exome Aggregation Consortium (ExAC) 0.00005
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MUTYH | - | - |
GRCh38 GRCh37 |
2686 | 2842 | |
TOE1 | - | - |
GRCh38 GRCh37 |
162 | 317 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Apr 26, 2024 | RCV000132425.24 | |
Uncertain significance (2) |
criteria provided, single submitter
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Nov 6, 2023 | RCV000212695.17 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Feb 5, 2024 | RCV000458224.24 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Oct 5, 2023 | RCV000656906.19 | |
Uncertain significance (1) |
criteria provided, single submitter
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Nov 24, 2021 | RCV002483273.8 | |
MUTYH-related disorder
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Uncertain significance (1) |
no assertion criteria provided
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Mar 14, 2024 | RCV004739462.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(Nov 06, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000919798.2
First in ClinVar: Jun 02, 2019 Last updated: Jan 06, 2024 |
Comment:
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 … (more)
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. (less)
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Uncertain significance
(May 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000685602.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces serine with tyrosine at codon 6 of the MUTYH protein. Computational prediction suggests that this variant may not impact protein structure … (more)
This missense variant replaces serine with tyrosine at codon 6 of the MUTYH protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 25186627). This variant has been identified in 27/280764 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Nov 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000545760.10
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 6 of the MUTYH protein (p.Ser6Tyr). … (more)
This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 6 of the MUTYH protein (p.Ser6Tyr). This variant is present in population databases (rs587782837, gnomAD 0.08%). This missense change has been observed in individual(s) with breast cancer (PMID: 25186627). ClinVar contains an entry for this variant (Variation ID: 142941). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain Significance
(Jan 11, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004835837.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
This missense variant replaces serine with tyrosine at codon 6 of the MUTYH protein. Computational prediction suggests that this variant may not impact protein structure … (more)
This missense variant replaces serine with tyrosine at codon 6 of the MUTYH protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 25186627). This variant has been identified in 27/280764 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 3
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Uncertain significance
(Feb 05, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Study: CSER-TexasKidsCanSeq
Accession: SCV001481434.3 First in ClinVar: Feb 27, 2021 Last updated: Jun 17, 2024 |
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Likely benign
(Apr 26, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000187518.10
First in ClinVar: Aug 06, 2014 Last updated: Aug 11, 2024 |
Comment:
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 … (more)
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. (less)
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Uncertain significance
(Nov 24, 2021)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Gastric cancer
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002789632.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Oct 05, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000211397.15
First in ClinVar: Feb 24, 2015 Last updated: Nov 25, 2023 |
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; Identified in individuals with breast or other cancers (PMID: 27720647, 25186627); This … (more)
In silico analysis supports that this missense variant does not alter protein structure/function; Identified in individuals with breast or other cancers (PMID: 27720647, 25186627); This variant is associated with the following publications: (PMID: 23108399, 25186627, 27720647) (less)
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Uncertain significance
(Feb 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001470569.3
First in ClinVar: Jan 26, 2021 Last updated: Jan 06, 2024 |
Comment:
The frequency of this variant in the general population, 0.00076 (27/35360 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the … (more)
The frequency of this variant in the general population, 0.00076 (27/35360 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with breast cancer (PMID: 25186627 (2015)). 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. (less)
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000691954.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
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Uncertain significance
(Mar 14, 2024)
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no assertion criteria provided
Method: clinical testing
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MUTYH-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000806352.2
First in ClinVar: Sep 13, 2018 Last updated: Oct 08, 2024 |
Comment:
The MUTYH c.17C>A variant is predicted to result in the amino acid substitution p.Ser6Tyr. This variant was observed in at least one individual who had … (more)
The MUTYH c.17C>A variant is predicted to result in the amino acid substitution p.Ser6Tyr. This variant was observed in at least one individual who had a hereditary cancer panel performed; however no information was provided to support its pathogenicity (Mu et al. 2016. PubMed ID: 27720647, Supplementary Table 3). This variant is reported in 0.076% of alleles in individuals of Latino descent in gnomAD and has been interpreted as variant of uncertain significance in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/142941/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Sanger Confirmation Is Required to Achieve Optimal Sensitivity and Specificity in Next-Generation Sequencing Panel Testing. | Mu W | The Journal of molecular diagnostics : JMD | 2016 | PMID: 27720647 |
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 |
Text-mined citations for rs587782837 ...
HelpRecord last updated Oct 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.