VCV000017588.2 - ClinVar

NM_001904.4(CTNNB1):c.134C>T (p.Ser45Phe)

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.

(13)

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/Likely pathogenic; other

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001904.4(CTNNB1):c.134C>T (p.Ser45Phe)

Variation ID: 17588 Accession: VCV000017588.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3p22.1 3: 41224646 (GRCh38) [ NCBI UCSC ] 3: 41266137 (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	Sep 10, 2016	Apr 18, 2021	Oct 30, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NM_001904.4:c.134C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001895.1:p.Ser45Phe	missense
NM_001098209.2:c.134C>T	NP_001091679.1:p.Ser45Phe	missense
NM_001098210.2:c.134C>T	NP_001091680.1:p.Ser45Phe	missense
NM_001330729.2:c.113C>T	NP_001317658.1:p.Ser38Phe	missense
NC_000003.12:g.41224646C>T
NC_000003.11:g.41266137C>T
NG_013302.2:g.30196C>T
LRG_1108:g.30196C>T
LRG_1108t1:c.134C>T	LRG_1108p1:p.Ser45Phe
	P35222:p.Ser45Phe

... more HGVS ... less HGVS

Protein change

S45F, S38F

Other names

Canonical SPDI

NC_000003.12:41224645:C:T

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

ClinGen: CA127283 UniProtKB: P35222#VAR_017631 OMIM: 116806.0013 dbSNP: rs121913409 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.
CTNNB1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	401	779
LOC126806658	-	-	-	GRCh38	-	226

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.
Hepatocellular carcinoma	Pathogenic/Likely pathogenic (2)	no assertion criteria provided	May 31, 2016	RCV000019153.7
Disease	Likely pathogenic (1)	no assertion criteria provided	Jul 14, 2015	RCV000423935.2
Transitional cell carcinoma of the bladder	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000422910.1
Prostate adenocarcinoma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000430307.1
Malignant neoplasm of body of uterus	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000418669.1
Neoplasm of the large intestine	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000429593.1
Malignant melanoma of skin	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000429678.1
Lung adenocarcinoma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000440570.1
Melanoma	Pathogenic (1)	no assertion criteria provided	Oct 2, 2014	RCV000436327.1
Nephroblastoma	other (1)	no assertion criteria provided	May 1, 2016	RCV000505673.1
Adrenal cortex carcinoma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000441643.1
Gallbladder cancer	Pathogenic (1)	no assertion criteria provided	Oct 30, 2020	RCV001374445.1
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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 (Jul 08, 1999)	no assertion criteria provided Method: literature only	HEPATOCELLULAR CARCINOMA, SOMATIC Affected status: not provided Allele origin: somatic	OMIM Accession: SCV000039441.2 First in ClinVar: Apr 04, 2013 Last updated: Sep 10, 2016	Publications: PubMed (1) PubMed: 10435629 Comment on evidence: In 4 cases of hepatocellular carcinoma (114550), Legoix et al. (1999) found a change in codon 45 of the CTNNB1 gene from TCT (ser) to … (more) In 4 cases of hepatocellular carcinoma (114550), Legoix et al. (1999) found a change in codon 45 of the CTNNB1 gene from TCT (ser) to TTT (phe). In 4 other cases, there was a ser45-to-pro mutation (116806.0014). (less)
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Neoplasm of the large intestine (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000503906.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000349496:c.134C>T
Pathogenic (Oct 02, 2014)	no assertion criteria provided Method: literature only	Melanoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000503907.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (7) PubMed: 11351304‚ 11930117‚ 15133491‚ 12124804‚ 9065403‚ 10027390‚ 11950921 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000349496:c.134C>T
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Malignant neoplasm of body of uterus (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000503908.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000349496:c.134C>T
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Adrenal cortex carcinoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000503913.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000349496:c.134C>T
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Prostate adenocarcinoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000503909.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000349496:c.134C>T
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	None (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000503910.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000349496:c.134C>T
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Transitional cell carcinoma of the bladder (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000503911.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000349496:c.134C>T
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Malignant melanoma of skin (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000503912.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000349496:c.134C>T
Likely pathogenic (Jul 14, 2015)	no assertion criteria provided Method: literature only	Disease (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000503914.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (2) PubMed: 24788118‚ 25157968 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000349496:c.134C>T
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Hepatocellular carcinoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000503915.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000349496:c.134C>T
other 2: Mutations in members of targetable cancer pathways, gene families, or functional groups, regardless of tumor type; (May 01, 2016)	no assertion criteria provided Method: clinical testing	WILMS TUMOR SOMATIC:c3267_wilms tumor (Somatic mutation) Affected status: yes Allele origin: somatic	Donald Williams Parsons Laboratory, Baylor College of Medicine Additional submitter: Donald Williams Parsons Laboratory, Baylor College of Medicine Study: CSER-BASIC3 Accession: SCV000599914.1 First in ClinVar: Sep 26, 2017 Last updated: Sep 26, 2017	Publications: PubMed (1) PubMed: 26822237
Pathogenic (Oct 30, 2020)	no assertion criteria provided Method: research	Gallbladder cancer Affected status: yes Allele origin: somatic	Institute of Medical Sciences, Banaras Hindu University Accession: SCV001571409.1 First in ClinVar: Apr 18, 2021 Last updated: Apr 18, 2021
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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

Title	Author	Journal	Year	Link
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.	Chang MT	Nature biotechnology	2016	PMID: 26619011
Prospective enterprise-level molecular genotyping of a cohort of cancer patients.	MacConaill LE	The Journal of molecular diagnostics : JMD	2014	PMID: 25157968
CTNNB1 S45F mutation predicts poor efficacy of meloxicam treatment for desmoid tumors: a pilot study.	Hamada S	PloS one	2014	PMID: 24788118
Genetic and epigenetic alterations of the APC gene in malignant melanoma.	Worm J	Oncogene	2004	PMID: 15133491
Molecular genetic analysis of malignant melanomas for aberrations of the WNT signaling pathway genes CTNNB1, APC, ICAT and BTRC.	Reifenberger J	International journal of cancer	2002	PMID: 12124804
Loss of membranous expression of beta-catenin is associated with tumor progression in cutaneous melanoma and rarely caused by exon 3 mutations.	Demunter A	Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc	2002	PMID: 11950921
Mutations in exon 3 of the beta-catenin gene are rare in melanoma cell lines.	Pollock PM	Melanoma research	2002	PMID: 11930117
Cytoplasmic and nuclear accumulation of beta-catenin is rarely caused by CTNNB1 exon 3 mutations in cutaneous malignant melanoma.	Omholt K	International journal of cancer	2001	PMID: 11351304
Beta-catenin mutations in hepatocellular carcinoma correlate with a low rate of loss of heterozygosity.	Legoix P	Oncogene	1999	PMID: 10435629
Frequent nuclear/cytoplasmic localization of beta-catenin without exon 3 mutations in malignant melanoma.	Rimm DL	The American journal of pathology	1999	PMID: 10027390
Stabilization of beta-catenin by genetic defects in melanoma cell lines.	Rubinfeld B	Science (New York, N.Y.)	1997	PMID: 9065403
http://docm.genome.wustl.edu/variants/ENST00000349496:c.134C>T	-	-	-	-
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Text-mined citations for rs121913409 ...

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 Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_001904.4(CTNNB1):c.134C>T (p.Ser45Phe)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs121913409 ...