VCV000631361.12 - ClinVar

NM_001048174.2(MUTYH):c.210del (p.Ser71fs)

Germline

Classification

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.

(3)

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.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001048174.2(MUTYH):c.210del (p.Ser71fs)

Variation ID: 631361 Accession: VCV000631361.12

Type and length

Deletion, 1 bp

Location

Cytogenetic: 1p34.1 1: 45333467 (GRCh38) [ NCBI UCSC ] 1: 45799139 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	May 20, 2019	Apr 20, 2024	Jun 5, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001048174.2:c.210del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001041639.1:p.Ser71fs	frameshift
NM_001128425.2:c.294del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001121897.1:p.Ser99fs	frameshift
NM_001048171.2:c.210del	NP_001041636.2:p.Ser71fs	frameshift
NM_001048172.2:c.213del	NP_001041637.1:p.Ser72fs	frameshift
NM_001048173.2:c.210del	NP_001041638.1:p.Ser71fs	frameshift
NM_001128425.1:c.294delG		frameshift
NM_001293190.2:c.255del	NP_001280119.1:p.Ser86fs	frameshift
NM_001293191.2:c.243del	NP_001280120.1:p.Ser82fs	frameshift
NM_001293192.2:c.-67del		5 prime UTR
NM_001293195.2:c.210del	NP_001280124.1:p.Ser71fs	frameshift
NM_001293196.2:c.-67del		5 prime UTR
NM_001350650.2:c.-62del		5 prime UTR
NM_001350651.2:c.-62del		5 prime UTR
NM_012222.3:c.285del	NP_036354.1:p.Ser96fs	frameshift
NR_146882.2:n.438del		non-coding transcript variant
NR_146883.2:n.361del		non-coding transcript variant
NC_000001.11:g.45333469del
NC_000001.10:g.45799141del
NG_008189.1:g.12004del
LRG_220:g.12004del
LRG_220t1:c.294del

... more HGVS ... less HGVS

Protein change

S71fs, S82fs, S86fs, S96fs, S72fs, S99fs

Other names

Canonical SPDI

NC_000001.11:45333466:CCC:CC

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

dbSNP: rs1557486313 ClinGen: CA913187555 VarSome

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
Gene	OMIM	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.
MUTYH		-	-	GRCh38 GRCh37	2740	2897

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.
Hereditary cancer-predisposing syndrome	Pathogenic (1)	criteria provided, single submitter	Apr 15, 2020	RCV000777549.4
Familial adenomatous polyposis 2	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jun 5, 2023	RCV001385505.9

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.
Pathogenic (Apr 15, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000913412.3 First in ClinVar: May 20, 2019 Last updated: Jan 12, 2022	Comment: This variant deletes 1 nucleotide in exon 3 of the MUTYH gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more) This variant deletes 1 nucleotide in exon 3 of the MUTYH gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MUTYH function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
Pathogenic (Nov 15, 2020)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Familial adenomatous polyposis 2 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001585383.4 First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024	Publications: PubMed (3) PubMed: 18534194‚ 20663686‚ 12606733 Comment: For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686). This variant has … (more) For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686). This variant has been observed in individual(s) with polyposis and colorectal cancer (PMID: 12606733). This variant is also known as 252delG in the literature. ClinVar contains an entry for this variant (Variation ID: 631361). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser99Alafs*3) in the MUTYH gene. It is expected to result in an absent or disrupted protein product. (less)
Pathogenic (Jun 05, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Familial adenomatous polyposis 2 (Autosomal recessive inheritance) Affected status: unknown Allele origin: germline	All of Us Research Program, National Institutes of Health Accession: SCV004837953.1 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)	Comment: This variant deletes 1 nucleotide in exon 3 of the MUTYH gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more) This variant deletes 1 nucleotide in exon 3 of the MUTYH gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MUTYH function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less) Number of individuals with the variant: 1 Zygosity: Single Heterozygote

Comment:

This variant deletes 1 nucleotide in exon 3 of the MUTYH gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MUTYH function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

Comment:

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686). This variant has been observed in individual(s) with polyposis and colorectal cancer (PMID: 12606733). This variant is also known as 252delG in the literature. ClinVar contains an entry for this variant (Variation ID: 631361). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser99Alafs*3) in the MUTYH gene. It is expected to result in an absent or disrupted protein product.

Comment:

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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
MUTYH-associated polyposis (MAP).	Nielsen M	Critical reviews in oncology/hematology	2011	PMID: 20663686
Characterization of mutant MUTYH proteins associated with familial colorectal cancer.	Ali M	Gastroenterology	2008	PMID: 18534194
Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH.	Sieber OM	The New England journal of medicine	2003	PMID: 12606733

Text-mined citations for rs1557486313 ...

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 Jan 13, 2025

ClinVar Genomic variation as it relates to human health

NM_001048174.2(MUTYH):c.210del (p.Ser71fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1557486313 ...