NM_000551.4(VHL):c.376_382delinsAA (p.Asp126fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 7, 2019
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:: RCV001248335.4

Allele description [Variation Report for NM_000551.4(VHL):c.376_382delinsAA (p.Asp126fs)]

NM_000551.4(VHL):c.376_382delinsAA (p.Asp126fs)

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:

Indel

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_000551.4(VHL):c.376_382delinsAA (p.Asp126fs)

HGVS:

NC_000003.12:g.10146549_10146555delinsAA
NG_008212.3:g.9915_9921delinsAA
NG_046756.1:g.4311_4317delinsAA
NM_000551.4:c.376_382delinsAAMANE SELECT
NM_001354723.2:c.*18-3238_*18-3232delinsAA
NM_198156.3:c.341-3238_341-3232delinsAA
NP_000542.1:p.Asp126fs
LRG_322t1:c.376_382delinsAA
LRG_322:g.9915_9921delinsAA
NC_000003.11:g.10188233_10188239delinsAA
NC_000003.11:g.10188233_10188239delinsAA
NM_000551.3:c.376_382delinsAA

Protein change:

D126fs

Links:

dbSNP: rs1696262643

NCBI 1000 Genomes Browser:

rs1696262643

Molecular consequence:

NM_000551.4:c.376_382delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354723.2:c.*18-3238_*18-3232delinsAA - intron variant - [Sequence Ontology: SO:0001627]
NM_198156.3:c.341-3238_341-3232delinsAA - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001421810	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 7, 2019)	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

SCV001421810

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 7, 2019)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001421810.3

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

Description

This variant has not been reported in the literature in individuals with VHL-related conditions. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in VHL are known to be pathogenic (PMID: 8956040, 12202531). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asp126Asnfs*4) in the VHL gene. It is expected to result in an absent or disrupted protein product.

#	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: Sep 29, 2024

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