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

Clinical significance:Pathogenic (Last evaluated: Jun 29, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001387330.1

Allele description [Variation Report for NM_000551.4(VHL):c.444del (p.Phe148fs)]

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:
Erythrocytosis, familial, 2 (ECYT2)
Synonyms:
POLYCYTHEMIA, CHUVASH TYPE; POLYCYTHEMIA, VHL-DEPENDENT
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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001587933Invitaecriteria provided, single submitter
Pathogenic
(Jun 29, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Detection of a germline mutation and somatic homozygous loss of the von Hippel-Lindau tumor-suppressor gene in a family with a de novo mutation. A combined genetic study, including cytogenetics, PCR/SSCP, FISH, and CGH.

Decker HJ, Neuhaus C, Jauch A, Speicher M, Ried T, Bujard M, Brauch H, Störkel S, Stöckle M, Seliger B, Huber C.

Hum Genet. 1996 Jun;97(6):770-6.

PubMed [citation]
PMID:
8641695

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
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001587933.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

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. This variant is not present in population databases (ExAC no frequency). 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 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. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 25, 2021

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