NM_000551.4(VHL):c.610G>T (p.Glu204Ter) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 19, 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:: RCV000631268.7

Allele description [Variation Report for NM_000551.4(VHL):c.610G>T (p.Glu204Ter)]

NM_000551.4(VHL):c.610G>T (p.Glu204Ter)

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:

single nucleotide variant

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_000551.4(VHL):c.610G>T (p.Glu204Ter)

Other names:

NM_000551.4(VHL):c.610G>T; p.Glu204Ter

HGVS:

NC_000003.12:g.10149933G>T
NG_008212.3:g.13299G>T
NG_046756.1:g.7695G>T
NM_000551.4:c.610G>TMANE SELECT
NM_001354723.2:c.*164G>T
NM_198156.3:c.487G>T
NP_000542.1:p.Glu204Ter
NP_000542.1:p.Glu204Ter
NP_937799.1:p.Glu163Ter
LRG_322t1:c.610G>T
LRG_322:g.13299G>T
LRG_322p1:p.Glu204Ter
NC_000003.11:g.10191617G>T
NM_000551.3:c.610G>T

Protein change:

E163*

Links:

dbSNP: rs758853661

NCBI 1000 Genomes Browser:

rs758853661

Molecular consequence:

NM_001354723.2:c.*164G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000551.4:c.610G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_198156.3:c.487G>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000752296	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 19, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 14691445, 14987375, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000752296

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 19, 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

Role of the C-terminal alpha-helical domain of the von Hippel-Lindau protein in its E3 ubiquitin ligase activity.

Lewis MD, Roberts BJ.

Oncogene. 2004 Mar 25;23(13):2315-23.

PubMed [citation]

PMID:: 14691445

Molecular pathology of von HippelLindau disease and the VHL tumour suppressor gene.

Richards FM.

Expert Rev Mol Med. 2001 Mar 19;2001:1-27. doi: 10.1017/S1462399401002654. No abstract available.

PubMed [citation]

PMID:: 14987375

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000752296.6

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is expected to delete a portion of the C-terminal region of the VHL protein near the Œ≤ domain (a-helix) (PMID: 14691445, 14987375). Experimental studies are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. This variant has not been reported in the literature in individuals with VHL-related disease. This variant is present in population databases (rs758853661, ExAC 0.009%). This sequence change results in a premature translational stop signal in the VHL gene (p.Glu204*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 10 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: Sep 29, 2024

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