NM_000551.4(VHL):c.390del (p.Asn131fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 7, 2018
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:: RCV002373128.2

Allele description [Variation Report for NM_000551.4(VHL):c.390del (p.Asn131fs)]

NM_000551.4(VHL):c.390del (p.Asn131fs)

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:

Deletion

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_000551.4(VHL):c.390del (p.Asn131fs)

HGVS:

NC_000003.12:g.10146563del
NG_008212.3:g.9929del
NG_046756.1:g.4325del
NM_000551.4:c.390delMANE SELECT
NM_001354723.2:c.*18-3224del
NM_198156.3:c.341-3224del
NP_000542.1:p.Asn131Thrfs
NP_000542.1:p.Asn131fs
LRG_322t1:c.390del
LRG_322:g.9929del
LRG_322p1:p.Asn131Thrfs
NC_000003.11:g.10188247del
NM_000551.3:c.390delT
NR_176335.1:n.719delT

Protein change:

N131fs

Molecular consequence:

NM_000551.4:c.390del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354723.2:c.*18-3224del - intron variant - [Sequence Ontology: SO:0001627]
NM_198156.3:c.341-3224del - intron variant - [Sequence Ontology: SO:0001627]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002624744	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jun 7, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15932632, 20151405 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002624744

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jun 7, 2018)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Prevalence of von Hippel-Lindau gene mutations in sporadic renal cell carcinoma: results from The Netherlands cohort study.

van Houwelingen KP, van Dijk BA, Hulsbergen-van de Kaa CA, Schouten LJ, Gorissen HJ, Schalken JA, van den Brandt PA, Oosterwijk E.

BMC Cancer. 2005 Jun 2;5:57.

PubMed [citation]

PMID:: 15932632
PMCID:: PMC1177929

Genetic analysis of von Hippel-Lindau disease.

Nordstrom-O'Brien M, van der Luijt RB, van Rooijen E, van den Ouweland AM, Majoor-Krakauer DF, Lolkema MP, van Brussel A, Voest EE, Giles RH.

Hum Mutat. 2010 May;31(5):521-37. doi: 10.1002/humu.21219.

PubMed [citation]

PMID:: 20151405

Details of each submission

From Ambry Genetics, SCV002624744.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The c.390delT pathogenic mutation, located in coding exon 2 of the VHL gene, results from a deletion of one nucleotide at nucleotide position 390, causing a translational frameshift with a predicted alternate stop codon (p.N131Tfs*28). This pathogenic mutation has been reported in an individual with sporadic renal clear-cell carcinoma (van Houwelingen KP et al. BMC Cancer. 2005 Jun;5:57; Nordstrom-O'Brien M et al. Hum. Mutat. 2010 May;31:521-37). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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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