This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 514 of the MUTYH protein (p.Ser514Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
ClinVar Genomic variation as it relates to human health
NM_001048174.2(MUTYH):c.1456T>C (p.Ser486Pro)
Germline
Classification
Help
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.
(2)
Help
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
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001048174.2(MUTYH):c.1456T>C (p.Ser486Pro)
Variation ID: 2901184 Accession: VCV002901184.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p34.1 1: 45329416 (GRCh38) [ NCBI UCSC ] 1: 45795088 (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 20, 2024 May 1, 2024 Oct 27, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001048174.2:c.1456T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001041639.1:p.Ser486Pro missense NM_001128425.2:c.1540T>C MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121897.1:p.Ser514Pro missense NM_001048171.2:c.1456T>C NP_001041636.2:p.Ser486Pro missense NM_001048172.2:c.1459T>C NP_001041637.1:p.Ser487Pro missense NM_001048173.2:c.1456T>C NP_001041638.1:p.Ser486Pro missense NM_001293190.2:c.1501T>C NP_001280119.1:p.Ser501Pro missense NM_001293191.2:c.1489T>C NP_001280120.1:p.Ser497Pro missense NM_001293192.2:c.1180T>C NP_001280121.1:p.Ser394Pro missense NM_001293195.2:c.1456T>C NP_001280124.1:p.Ser486Pro missense NM_001293196.2:c.1180T>C NP_001280125.1:p.Ser394Pro missense NM_001350650.2:c.1111T>C NP_001337579.1:p.Ser371Pro missense NM_001350651.2:c.1111T>C NP_001337580.1:p.Ser371Pro missense NM_001407069.1:c.1489T>C NP_001393998.1:p.Ser497Pro missense NM_001407070.1:c.1456T>C NP_001393999.1:p.Ser486Pro missense NM_001407071.1:c.1459T>C NP_001394000.1:p.Ser487Pro missense NM_001407072.1:c.1456T>C NP_001394001.1:p.Ser486Pro missense NM_001407073.1:c.1456T>C NP_001394002.1:p.Ser486Pro missense NM_001407075.1:c.1372T>C NP_001394004.1:p.Ser458Pro missense NM_001407077.1:c.1489T>C NP_001394006.1:p.Ser497Pro missense NM_001407078.1:c.1459T>C NP_001394007.1:p.Ser487Pro missense NM_001407079.1:c.1417T>C NP_001394008.1:p.Ser473Pro missense NM_001407080.1:c.1414T>C NP_001394009.1:p.Ser472Pro missense NM_001407081.1:c.1456T>C NP_001394010.1:p.Ser486Pro missense NM_001407082.1:c.1111T>C NP_001394011.1:p.Ser371Pro missense NM_001407083.1:c.1498T>C NP_001394012.1:p.Ser500Pro missense NM_001407085.1:c.1498T>C NP_001394014.1:p.Ser500Pro missense NM_001407086.1:c.1459T>C NP_001394015.1:p.Ser487Pro missense NM_001407087.1:c.1477T>C NP_001394016.1:p.Ser493Pro missense NM_001407088.1:c.1456T>C NP_001394017.1:p.Ser486Pro missense NM_001407089.1:c.1456T>C NP_001394018.1:p.Ser486Pro missense NM_001407091.1:c.1180T>C NP_001394020.1:p.Ser394Pro missense NM_012222.3:c.1531T>C NP_036354.1:p.Ser511Pro missense NR_146882.2:n.1864T>C non-coding transcript variant NR_146883.2:n.1713T>C non-coding transcript variant NR_176269.1:n.1860T>C non-coding transcript variant NR_176270.1:n.1800T>C NR_176271.1:n.1723T>C non-coding transcript variant NR_176272.1:n.1787T>C non-coding transcript variant NR_176273.1:n.1745T>C non-coding transcript variant NR_176274.1:n.1800T>C non-coding transcript variant NC_000001.11:g.45329416A>G NC_000001.10:g.45795088A>G NG_008189.1:g.16055T>C NG_090898.1:g.62A>G LRG_220:g.16055T>C LRG_220t1:c.1540T>C LRG_220p1:p.Ser514Pro - Protein change
- S487P, S511P, S394P, S458P, S472P, S473P, S500P, S514P, S371P, S486P, S493P, S497P, S501P
- Other names
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- Canonical SPDI
- NC_000001.11:45329415:A:G
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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.
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- Links
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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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 |
2690 | 2846 | |
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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
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Oct 27, 2023 | RCV003615287.2 | |
| Uncertain significance (1) |
criteria provided, single submitter
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Dec 15, 2020 | RCV004374165.1 |
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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|---|---|---|---|---|---|
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Uncertain significance
(Oct 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: SCV004529953.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 514 of the MUTYH protein (p.Ser514Pro). … (more)
This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 514 of the MUTYH protein (p.Ser514Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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
(Dec 15, 2020)
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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: SCV004936858.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The c.1540T>C (p.S514P) alteration is located in exon 16 (coding exon 16) of the MUTYH gene. This alteration results from a T to C substitution … (more)
The c.1540T>C (p.S514P) alteration is located in exon 16 (coding exon 16) of the MUTYH gene. This alteration results from a T to C substitution at nucleotide position 1540, causing the serine (S) at amino acid position 514 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
|
Comment:
Comment:
The c.1540T>C (p.S514P) alteration is located in exon 16 (coding exon 16) of the MUTYH gene. This alteration results from a T to C substitution at nucleotide position 1540, causing the serine (S) at amino acid position 514 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
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. |
Comment:
This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 514 of the MUTYH protein (p.Ser514Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Comment:
The c.1540T>C (p.S514P) alteration is located in exon 16 (coding exon 16) of the MUTYH gene. This alteration results from a T to C substitution at nucleotide position 1540, causing the serine (S) at amino acid position 514 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated Sep 30, 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.