NM_000551.4(VHL):c.606dup (p.Gln203fs) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 10, 2024
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:: RCV001203962.8

Allele description [Variation Report for NM_000551.4(VHL):c.606dup (p.Gln203fs)]

NM_000551.4(VHL):c.606dup (p.Gln203fs)

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:

Duplication

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_000551.4(VHL):c.606dup (p.Gln203fs)

HGVS:

NC_000003.12:g.10149929dup
NG_008212.3:g.13295dup
NG_046756.1:g.7691dup
NM_000551.4:c.606dupMANE SELECT
NM_001354723.2:c.*160dup
NM_198156.3:c.483dup
NP_000542.1:p.Gln203fs
NP_937799.1:p.Gln162fs
LRG_322t1:c.606dup
LRG_322:g.13295dup
NC_000003.11:g.10191612_10191613insA
NC_000003.11:g.10191613dup
NM_000551.3:c.606dup

Protein change:

Q162fs

Links:

dbSNP: rs1696365502

NCBI 1000 Genomes Browser:

rs1696365502

Molecular consequence:

NM_001354723.2:c.*160dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000551.4:c.606dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_198156.3:c.483dup - 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
SCV001375147	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 10, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17024664, 22799452, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001375147

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 10, 2024)

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

Genotype-phenotype correlations in von Hippel-Lindau disease.

Ong KR, Woodward ER, Killick P, Lim C, Macdonald F, Maher ER.

Hum Mutat. 2007 Feb;28(2):143-9.

PubMed [citation]

PMID:: 17024664

Identification of 3 novel VHL germ-line mutations in Danish VHL patients.

Dandanell M, Friis-Hansen L, Sunde L, Nielsen FC, Hansen TV.

BMC Med Genet. 2012 Jul 16;13:54.

PubMed [citation]

PMID:: 22799452
PMCID:: PMC3458949

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001375147.5

#	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 results in a frameshift in the VHL gene (p.Gln203Thrfs*53). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 11 amino acid(s) of the VHL protein and extend the protein by 41 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This frameshift has been observed in individual(s) with clinical features of von Hippel-Lindau syndrome (PMID: 17024664, 22799452; Invitae). This variant is also known as 819_820dupA. ClinVar contains an entry for this variant (Variation ID: 935385). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. RNA analysis provides insufficient evidence to determine the effect of this variant on VHL splicing (Invitae). 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.

#	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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