NM_000551.4(VHL):c.241_244dup (p.Arg82fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 1, 2023
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:: RCV001384689.4

Allele description [Variation Report for NM_000551.4(VHL):c.241_244dup (p.Arg82fs)]

NM_000551.4(VHL):c.241_244dup (p.Arg82fs)

Gene:

VHL:von Hippel-Lindau tumor suppressor [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_000551.4(VHL):c.241_244dup (p.Arg82fs)

HGVS:

NC_000003.12:g.10142088_10142091dup
NG_008212.3:g.5454_5457dup
NM_000551.4:c.241_244dupMANE SELECT
NM_001354723.2:c.241_244dup
NM_198156.3:c.241_244dup
NP_000542.1:p.Arg82fs
NP_001341652.1:p.Arg82fs
NP_937799.1:p.Arg82fs
LRG_322:g.5454_5457dup
NC_000003.11:g.10183771_10183772insCCGC
NC_000003.11:g.10183772_10183775dup

Protein change:

R82fs

Links:

dbSNP: rs2125125103

NCBI 1000 Genomes Browser:

rs2125125103

Molecular consequence:

NM_000551.4:c.241_244dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354723.2:c.241_244dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_198156.3:c.241_244dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001584261	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 1, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 8956040, 12202531, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001584261

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 1, 2023)

germline

clinical testing

PubMed (3)
[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

Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan.

Zbar B, Kishida T, Chen F, Schmidt L, Maher ER, Richards FM, Crossey PA, Webster AR, Affara NA, Ferguson-Smith MA, Brauch H, Glavac D, Neumann HP, Tisherman S, Mulvihill JJ, Gross DJ, Shuin T, Whaley J, Seizinger B, Kley N, Olschwang S, Boisson C, et al.

Hum Mutat. 1996;8(4):348-57.

PubMed [citation]

PMID:: 8956040

Retinal hemangioblastoma in von Hippel-Lindau disease: a clinical and molecular study.

Dollfus H, Massin P, Taupin P, Nemeth C, Amara S, Giraud S, Béroud C, Dureau P, Gaudric A, Landais P, Richard S.

Invest Ophthalmol Vis Sci. 2002 Sep;43(9):3067-74.

PubMed [citation]

PMID:: 12202531

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001584261.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Arg82Profs*51) in the VHL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in VHL are known to be pathogenic (PMID: 8956040, 12202531). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with VHL-related conditions. ClinVar contains an entry for this variant (Variation ID: 1072069). For these reasons, this variant has been classified as Pathogenic.

#	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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