VCV000421902.14 - ClinVar

NM_000546.6(TP53):c.327_328del (p.Phe109fs)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic/Likely pathogenic
Pathogenic (1); Likely pathogenic (3)

4 out of 4 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000546.6(TP53):c.327_328del (p.Phe109fs)

Variation ID: 421902 Accession: VCV000421902.14

Type and length

Deletion, 2 bp

Location

Cytogenetic: 17p13.1 17: 7676041-7676042 (GRCh38) [ NCBI UCSC ] 17: 7579359-7579360 (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	Apr 27, 2017	Feb 15, 2026	Jun 18, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_000546.6:c.327_328del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000537.3:p.Phe109fs	frameshift
NM_001126112.3:c.327_328del	NP_001119584.1:p.Phe109fs	frameshift
NM_001126113.3:c.327_328del	NP_001119585.1:p.Phe109fs	frameshift
NM_001126114.3:c.327_328del	NP_001119586.1:p.Phe109fs	frameshift
NM_001126118.2:c.210_211del	NP_001119590.1:p.Phe70fs	frameshift
NM_001276695.3:c.210_211del	NP_001263624.1:p.Phe70fs	frameshift
NM_001276696.3:c.210_211del	NP_001263625.1:p.Phe70fs	frameshift
NM_001276760.3:c.210_211del	NP_001263689.1:p.Phe70fs	frameshift
NM_001276761.3:c.210_211del	NP_001263690.1:p.Phe70fs	frameshift
NC_000017.11:g.7676041_7676042del
NC_000017.10:g.7579359_7579360del
NG_017013.2:g.16509_16510del
LRG_321:g.16509_16510del
LRG_321t1:c.327_328del	LRG_321p1:p.Phe109fs

... more HGVS ... less HGVS

Protein change

F109fs, F70fs

Other names

Canonical SPDI

NC_000017.11:7676040:GG:

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: CA16620636 dbSNP: rs1064795434 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.
TP53		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	3915	4016

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.
not provided	Likely pathogenic (1)	criteria provided, single submitter	Aug 4, 2016	RCV000479264.2
Li-Fraumeni syndrome	Pathogenic (1)	criteria provided, single submitter	Dec 22, 2019	RCV001053810.11
Li-Fraumeni syndrome 1	Likely pathogenic (1)	criteria provided, single submitter	Jun 18, 2022	RCV002289640.2
Hereditary cancer-predisposing syndrome	Likely pathogenic (1)	criteria provided, single submitter	Jun 18, 2022	RCV002289641.2

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.	Expand all rows Collapse all rows 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.
Likely pathogenic (Aug 04, 2016) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015))	not provided	GeneDx Accession: SCV000571235.3 First in ClinVar: Apr 27, 2017 Last updated: Apr 27, 2017	Comment: show This deletion of two nucleotides in TP53 is denoted c.327_328delCC at the cDNA level and p.Phe109LeufsX39 (F109LfsX39) at the protein level. The normal sequence, with the bases that are deleted in braces, is GTTT[CC]GTCT. The deletion causes a frameshift which changes a Phenylalanine to a Leucine at codon 109, and creates a premature stop codon at position 39 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, we consider this deletion to be a likely pathogenic variant. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (Dec 22, 2019) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Li-Fraumeni syndrome	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001218091.8 First in ClinVar: Apr 15, 2020 Last updated: Feb 15, 2026	Publications: PubMed (1) PubMed: 20522432 Comment: show For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). This variant has not been reported in the literature in individuals with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 421902). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe109Leufs*39) in the TP53 gene. It is expected to result in an absent or disrupted protein product. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely pathogenic (Jun 18, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Li-Fraumeni syndrome 1	Genome-Nilou Lab Accession: SCV002583071.1 First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Likely pathogenic (Jun 18, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hereditary cancer-predisposing syndrome	Genome-Nilou Lab Accession: SCV002582409.1 First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Comment:

This deletion of two nucleotides in TP53 is denoted c.327_328delCC at the cDNA level and p.Phe109LeufsX39 (F109LfsX39) at the protein level. The normal sequence, with the bases that are deleted in braces, is GTTT[CC]GTCT. The deletion causes a frameshift which changes a Phenylalanine to a Leucine at codon 109, and creates a premature stop codon at position 39 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, we consider this deletion to be a likely pathogenic variant.

Comment:

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). This variant has not been reported in the literature in individuals with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 421902). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe109Leufs*39) in the TP53 gene. It is expected to result in an absent or disrupted protein product.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes.	Ruijs MW	Journal of medical genetics	2010	PMID: 20522432

Text-mined citations for rs1064795434 ...

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 Apr 13, 2026