NM_000551.4(VHL):c.444del (p.Phe148fs) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 29, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001387330.6

Allele description

NM_000551.4(VHL):c.444del (p.Phe148fs)

Genes:

LOC107303340:3p25 von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase Alu-mediated recombination region [Gene]
VHL:von Hippel-Lindau tumor suppressor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_000551.4(VHL):c.444del (p.Phe148fs)

HGVS:

NC_000003.12:g.10146617del
NG_008212.3:g.9983del
NG_046756.1:g.4379del
NM_000551.4:c.444delMANE SELECT
NM_001354723.2:c.*18-3170del
NM_198156.3:c.341-3170del
NP_000542.1:p.Phe148fs
LRG_322:g.9983del
NC_000003.11:g.10188297del
NC_000003.11:g.10188301del
NM_000551.3:c.444delT
p.[Phe148Leufs*11]

Protein change:

F148fs

Links:

dbSNP: rs869025653

NCBI 1000 Genomes Browser:

rs869025653

Molecular consequence:

NM_000551.4:c.444del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354723.2:c.*18-3170del - intron variant - [Sequence Ontology: SO:0001627]
NM_198156.3:c.341-3170del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Chuvash polycythemia
Synonyms:: POLYCYTHEMIA, VHL-DEPENDENT; Erythrocytosis, familial, 2
Identifiers:: MONDO: MONDO:0009892; MedGen: C1837915; Orphanet: 238557; OMIM: 263400

Name:: Von Hippel-Lindau syndrome (VHLS)
Synonyms:: VHL syndrome; Von Hippel-Lindau
Identifiers:: MONDO: MONDO:0008667; MedGen: C0019562; Orphanet: 892; OMIM: 193300

Recent activity

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MULTISPECIES: molybdate ABC transporter substrate-binding protein [Rahnella]
MULTISPECIES: molybdate ABC transporter substrate-binding protein [Rahnella]
gi|503341743|ref|WP_013576404.1|

Protein
PREDICTED: Zea mays cinnamoyl CoA reductase 1 (LOC542463), transcript variant X1...
PREDICTED: Zea mays cinnamoyl CoA reductase 1 (LOC542463), transcript variant X1, mRNA
gi|1897951603|ref|XM_008650570.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001587933	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 29, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 8707293, 10567493, 11309459, 8641695, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001587933

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 29, 2020)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the VHL tumor suppressor gene and associated lesions in families with von Hippel-Lindau disease from central Europe.

Glavac D, Neumann HP, Wittke C, Jaenig H, Masek O, Streicher T, Pausch F, Engelhardt D, Plate KH, Höfler H, Chen F, Zbar B, Brauch H.

Hum Genet. 1996 Sep;98(3):271-80.

PubMed [citation]

PMID:: 8707293

The impact of molecular genetic analysis of the VHL gene in patients with haemangioblastomas of the central nervous system.

Gläsker S, Bender BU, Apel TW, Natt E, van Velthoven V, Scheremet R, Zentner J, Neumann HP.

J Neurol Neurosurg Psychiatry. 1999 Dec;67(6):758-62.

PubMed [citation]

PMID:: 10567493
PMCID:: PMC1736691

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001587933.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the VHL protein. Other variant(s) that disrupt this region (p.Ser183*) have been determined to be pathogenic (PMID: 8707293, 10567493, 11309459). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has been reported in individual(s) with clinical features of von Hippel-Lindau syndrome (PMID: 8641695). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 223212). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the VHL gene (p.Phe148Leufs*11). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 66 amino acids of the VHL protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2024

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