ClinVar Genomic variation as it relates to human health
NM_001048174.2(MUTYH):c.1112_1119del (p.Ala371fs)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001048174.2(MUTYH):c.1112_1119del (p.Ala371fs)
Variation ID: 2031935 Accession: VCV002031935.2
- Type and length
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Deletion, 8 bp
- Location
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Cytogenetic: 1p34.1 1: 45331540-45331547 (GRCh38) [ NCBI UCSC ] 1: 45797212-45797219 (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 8, 2023 Feb 20, 2024 Sep 22, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001048174.2:c.1112_1119del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001041639.1:p.Ala371fs frameshift NM_001128425.2:c.1196_1203del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121897.1:p.Ala399fs frameshift NM_001048171.2:c.1112_1119del NP_001041636.2:p.Ala371fs frameshift NM_001048172.2:c.1115_1122del NP_001041637.1:p.Ala372fs frameshift NM_001048173.2:c.1112_1119del NP_001041638.1:p.Ala371fs frameshift NM_001293190.2:c.1157_1164del NP_001280119.1:p.Ala386fs frameshift NM_001293191.2:c.1145_1152del NP_001280120.1:p.Ala382fs frameshift NM_001293192.2:c.836_843del NP_001280121.1:p.Ala279fs frameshift NM_001293195.2:c.1112_1119del NP_001280124.1:p.Ala371fs frameshift NM_001293196.2:c.836_843del NP_001280125.1:p.Ala279fs frameshift NM_001350650.2:c.767_774del NP_001337579.1:p.Ala256fs frameshift NM_001350651.2:c.767_774del NP_001337580.1:p.Ala256fs frameshift NM_001407069.1:c.1144_1151delGCAGGACT NP_001393998.1:p.Ala382Valfs frameshift NM_001407070.1:c.1111_1118delGCAGGACT NP_001393999.1:p.Ala371Valfs frameshift NM_001407071.1:c.1114_1121delGCAGGACT NP_001394000.1:p.Ala372Valfs frameshift NM_001407072.1:c.1111_1118delGCAGGACT NP_001394001.1:p.Ala371Valfs frameshift NM_001407073.1:c.1111_1118delGCAGGACT NP_001394002.1:p.Ala371Valfs frameshift NM_001407075.1:c.1027_1034delGCAGGACT NP_001394004.1:p.Ala343Valfs frameshift NM_001407077.1:c.1144_1151delGCAGGACT NP_001394006.1:p.Ala382Valfs frameshift NM_001407078.1:c.1114_1121delGCAGGACT NP_001394007.1:p.Ala372Valfs frameshift NM_001407079.1:c.1072_1079delGCAGGACT NP_001394008.1:p.Ala358Valfs frameshift NM_001407080.1:c.1069_1076delGCAGGACT NP_001394009.1:p.Ala357Valfs frameshift NM_001407081.1:c.1111_1118delGCAGGACT NP_001394010.1:p.Ala371Valfs frameshift NM_001407082.1:c.766_773delGCAGGACT NP_001394011.1:p.Ala256Valfs frameshift NM_001407083.1:c.1153_1160delGCAGGACT NP_001394012.1:p.Ala385Valfs frameshift NM_001407085.1:c.1153_1160delGCAGGACT NP_001394014.1:p.Ala385Valfs frameshift NM_001407086.1:c.1114_1121delGCAGGACT NP_001394015.1:p.Ala372Valfs frameshift NM_001407087.1:c.1132_1139delGCAGGACT NP_001394016.1:p.Ala378Valfs frameshift NM_001407088.1:c.1111_1118delGCAGGACT NP_001394017.1:p.Ala371Valfs frameshift NM_001407089.1:c.1111_1118delGCAGGACT NP_001394018.1:p.Ala371Valfs frameshift NM_001407091.1:c.835_842delGCAGGACT NP_001394020.1:p.Ala279Valfs frameshift NM_012222.3:c.1187_1194del NP_036354.1:p.Ala396fs frameshift NR_146882.2:n.1340_1347del non-coding transcript variant NR_146883.2:n.1189_1196del non-coding transcript variant NR_176269.1:n.1335_1342delGCAGGACT NR_176270.1:n.1275_1282delGCAGGACT NR_176271.1:n.1198_1205delGCAGGACT NR_176272.1:n.1262_1269delGCAGGACT NR_176273.1:n.1220_1227delGCAGGACT NR_176274.1:n.1275_1282delGCAGGACT NC_000001.11:g.45331541_45331548del NC_000001.10:g.45797213_45797220del NG_008189.1:g.13924_13931del LRG_220:g.13924_13931del LRG_220t1:c.1195_1202del LRG_220p1:p.Ala399Valfs - Protein change
- A256fs, A279fs, A386fs, A371fs, A396fs, A372fs, A382fs, A399fs
- Other names
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- Canonical SPDI
- NC_000001.11:45331539:CAGTCCTGC:C
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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
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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
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Pathogenic (1) |
criteria provided, single submitter
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Sep 22, 2022 | RCV002898965.3 |
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
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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
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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
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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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Pathogenic
(Sep 22, 2022)
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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: SCV003238668.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MUTYH protein in which other variant(s) (p.Pro405Leu) have … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MUTYH protein in which other variant(s) (p.Pro405Leu) have been determined to be pathogenic (PMID: 16140997, 16557584, 16616356, 17161978, 19732775, 19836313, 20191381, 20848659, 23322991, 25820570). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala399Valfs*130) in the MUTYH gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 151 amino acid(s) of the MUTYH protein. (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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Functional Complementation Assay for 47 MUTYH Variants in a MutY-Disrupted Escherichia coli Strain. | Komine K | Human mutation | 2015 | PMID: 25820570 |
Impaired suppressive activities of human MUTYH variant proteins against oxidative mutagenesis. | Shinmura K | World journal of gastroenterology | 2012 | PMID: 23322991 |
Adenine DNA glycosylase activity of 14 human MutY homolog (MUTYH) variant proteins found in patients with colorectal polyposis and cancer. | Goto M | Human mutation | 2010 | PMID: 20848659 |
Increased MUTYH mutation frequency among Dutch families with breast cancer and colorectal cancer. | Wasielewski M | Breast cancer research and treatment | 2010 | PMID: 20191381 |
Adenine removal activity and bacterial complementation with the human MutY homologue (MUTYH) and Y165C, G382D, P391L and Q324R variants associated with colorectal cancer. | Kundu S | DNA repair | 2009 | PMID: 19836313 |
Expanded extracolonic tumor spectrum in MUTYH-associated polyposis. | Vogt S | Gastroenterology | 2009 | PMID: 19732775 |
MUTYH-associated polyposis--from defect in base excision repair to clinical genetic testing. | Cheadle JP | DNA repair | 2007 | PMID: 17161978 |
Novel findings in Swedish patients with MYH-associated polyposis: mutation detection and clinical characterization. | Kanter-Smoler G | Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | 2006 | PMID: 16616356 |
MUTYH-associated polyposis: 70 of 71 patients with biallelic mutations present with an attenuated or atypical phenotype. | Aretz S | International journal of cancer | 2006 | PMID: 16557584 |
Multiplicity in polyp count and extracolonic manifestations in 40 Dutch patients with MYH associated polyposis coli (MAP). | Nielsen M | Journal of medical genetics | 2005 | PMID: 16140997 |
Text-mined citations for this variant ...
HelpRecord last updated Sep 29, 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.