VCV000231649.19 - ClinVar

NM_000314.8(PTEN):c.17_18del (p.Lys6fs)

Germline

Classification

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

Pathogenic

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_000314.8(PTEN):c.17_18del (p.Lys6fs)

Variation ID: 231649 Accession: VCV000231649.19

Type and length

Deletion, 2 bp

Location

Cytogenetic: 10q23.31 10: 87864485-87864486 (GRCh38) [ NCBI UCSC ] 10: 89624242-89624243 (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 29, 2016	Feb 15, 2026	Mar 23, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000314.8:c.17_18del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000305.3:p.Lys6fs	frameshift
NM_001304717.5:c.536_537del	NP_001291646.4:p.Lys179fs	frameshift
NM_001304718.2:c.-689_-688del		5 prime UTR
NC_000010.11:g.87864486_87864487del
NC_000010.10:g.89624243_89624244del
NG_007466.2:g.6048_6049del
NG_033079.1:g.3952_3953del
LRG_1087:g.3952_3953del
LRG_311:g.6048_6049del
LRG_311t1:c.17_18del

... more HGVS ... less HGVS

Protein change

K179fs, K6fs

Other names

Canonical SPDI

NC_000010.11:87864484:AAA:A

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: CA10577412 dbSNP: rs121913290 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.
PTEN		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	3595	4131

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	Jul 21, 2023	RCV000215567.4
not provided	Pathogenic (1)	criteria provided, single submitter	Mar 23, 2024	RCV000222693.4
PTEN hamartoma tumor syndrome	Pathogenic (1)	criteria provided, single submitter	Oct 16, 2022	RCV000804226.9
Cowden syndrome 1	Pathogenic (1)	criteria provided, single submitter	Sep 25, 2023	RCV003454634.1

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.	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.
Pathogenic (Jul 21, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Hereditary cancer-predisposing syndrome	Ambry Genetics Accession: SCV000275559.9 First in ClinVar: May 29, 2016 Last updated: May 01, 2024	Comment: show The c.17_18delAA pathogenic mutation, located in coding exon 1 of the PTEN gene, results from a deletion of two nucleotides at nucleotide positions 17 to 18, causing a translational frameshift with a predicted alternate stop codon (p.K6Rfs*4). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with PTEN-related disease (Ambry internal data). This mutation was detected in a patient with Lhermitte-Duclos disease (Zhou et al. Am J Hum Genet 2003 Nov; 73(5): 1191-8). This mutation is also known as 16-17delAA in the published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (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

Pathogenic (Mar 23, 2024) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV000279972.10 First in ClinVar: May 29, 2016 Last updated: Sep 29, 2024	Comment: show Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29496690, 34184188, 26641771, 35227301, 20049735, 14566704, 26342236, 22460905, 36453251) (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 (Oct 16, 2022) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	PTEN hamartoma tumor syndrome	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000944123.6 First in ClinVar: Aug 14, 2019 Last updated: Feb 15, 2026	Publications: PubMed (4) PubMed: 21194675‚ 29496690‚ 34184188‚ 9467011 Comment: show This sequence change creates a premature translational stop signal (p.Lys6Argfs*4) in the PTEN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of PTEN hamartoma tumor syndrome (PMID: 29496690, 34184188). ClinVar contains an entry for this variant (Variation ID: 231649). For these reasons, this variant has been classified as Pathogenic. (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

Pathogenic (Sep 25, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Cowden syndrome 1	Myriad Genetics, Inc. Accession: SCV004189746.1 First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023	Comment: show This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Comment:

The c.17_18delAA pathogenic mutation, located in coding exon 1 of the PTEN gene, results from a deletion of two nucleotides at nucleotide positions 17 to 18, causing a translational frameshift with a predicted alternate stop codon (p.K6Rfs*4). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with PTEN-related disease (Ambry internal data). This mutation was detected in a patient with Lhermitte-Duclos disease (Zhou et al. Am J Hum Genet 2003 Nov; 73(5): 1191-8). This mutation is also known as 16-17delAA in the published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

Comment:

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29496690, 34184188, 26641771, 35227301, 20049735, 14566704, 26342236, 22460905, 36453251)

Comment:

This sequence change creates a premature translational stop signal (p.Lys6Argfs*4) in the PTEN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of PTEN hamartoma tumor syndrome (PMID: 29496690, 34184188). ClinVar contains an entry for this variant (Variation ID: 231649). For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
"Thyroid nodular disease and PTEN mutation in a multicentre series of children with PTEN hamartoma tumor syndrome (PHTS)".	Tuli G	Endocrine	2021	PMID: 34184188
Novel Germline PTEN Mutation Associated with Cowden Syndrome and Osteosarcoma.	Lopez C	Cancer genomics & proteomics	2018	PMID: 29496690
A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands.	Tan MH	American journal of human genetics	2011	PMID: 21194675
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation.	Marsh DJ	Human molecular genetics	1998	PMID: 9467011

Text-mined citations for rs121913290 ...

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