NM_000551.4(VHL):c.607_608del (p.Gln203fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 11, 2021
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:: RCV002359943.2

Allele description [Variation Report for NM_000551.4(VHL):c.607_608del (p.Gln203fs)]

NM_000551.4(VHL):c.607_608del (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:

Microsatellite

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_000551.4(VHL):c.607_608del (p.Gln203fs)

HGVS:

NC_000003.12:g.10149928CA[1]
NG_008212.3:g.13294CA[1]
NG_046756.1:g.7690CA[1]
NM_000551.4:c.607_608delMANE SELECT
NM_001354723.2:c.*159CA[1]
NM_198156.3:c.484_485del
NP_000542.1:p.Gln203Glyfs
NP_000542.1:p.Gln203fs
NP_937799.1:p.Gln162fs
LRG_322t1:c.605_606CA[1]
LRG_322:g.13294CA[1]
LRG_322p1:p.Gln203Glyfs
NC_000003.11:g.10191612CA[1]
NM_000551.3:c.605_606CA[1]
NM_000551.3:c.607_608delCA
NR_176335.1:n.934_935CA[1]

Protein change:

Q162fs

Molecular consequence:

NM_001354723.2:c.*159CA[1] - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000551.4:c.607_608del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_198156.3:c.484_485del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

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host cell factor 1b isoform X1 [Xiphias gladius]
host cell factor 1b isoform X1 [Xiphias gladius]
gi|2007664622|ref|XP_040009177.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002657720	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Nov 11, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12202531, 15300849, 32980744 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002657720

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Nov 11, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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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

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

Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions.

Gallou C, Chauveau D, Richard S, Joly D, Giraud S, Olschwang S, Martin N, Saquet C, Chrétien Y, Méjean A, Correas JM, Benoît G, Colombeau P, Grünfeld JP, Junien C, Béroud C.

Hum Mutat. 2004 Sep;24(3):215-24. Erratum in: Hum Mutat. 2004 Nov;24(5):435-6.

PubMed [citation]

PMID:: 15300849

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002657720.2

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

Description

The c.607_608delCA variant, located in coding exon 3 of the VHL gene, results from a deletion of two nucleotides at nucleotide positions 607 to 608, causing a translational frameshift with a predicted alternate stop codon (p.Q203Gfs*52). This alteration occurs at the 3' terminus of theVHL gene, is not expected to trigger nonsense-mediated mRNAdecay and results in the elongation of the protein by 40 amino acids. This frameshift impacts the last 5%, 11 amino acids, of the native protein. However, frameshifts are typically deleterious in nature. This variant has been reported in three individuals from one family with von Hippel-Lindau (Dollfus H et al. Invest Ophthalmol Vis Sci, 2002 Sep;43:3067-74; Gallou C et al. Hum Mutat, 2004 Sep;24:215-24). In addition, this alteration has been observed in at least one individual with a personal and/or family history that is consistent with VHL-related disease (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be 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: May 1, 2024

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