NM_000551.4(VHL):c.192del (p.Ser65fs) AND Von Hippel-Lindau syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 3, 2016
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:: RCV000586821.1

Allele description [Variation Report for NM_000551.4(VHL):c.192del (p.Ser65fs)]

NM_000551.4(VHL):c.192del (p.Ser65fs)

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.192del (p.Ser65fs)

HGVS:

NC_000003.12:g.10142039del
NG_008212.3:g.5405del
NM_000551.4:c.192delMANE SELECT
NM_001354723.2:c.192del
NM_198156.3:c.192del
NP_000542.1:p.Ser65fs
NP_001341652.1:p.Ser65fs
NP_937799.1:p.Ser65fs
LRG_322:g.5405del
NC_000003.11:g.10183723del
NM_000551.3:c.192delC
p.S65RfsX2

Protein change:

S65fs

Links:

dbSNP: rs730882031

NCBI 1000 Genomes Browser:

rs730882031

Molecular consequence:

NM_000551.4:c.192del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354723.2:c.192del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_198156.3:c.192del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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
SCV000697484	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Feb 3, 2016)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20151405, 8187067, 9143408 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000697484

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Feb 3, 2016)

germline

clinical testing

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

LabCorp Variant Classification Summary - May 2015.docx

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

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

Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas.

Shuin T, Kondo K, Torigoe S, Kishida T, Kubota Y, Hosaka M, Nagashima Y, Kitamura H, Latif F, Zbar B, et al.

Cancer Res. 1994 Jun 1;54(11):2852-5.

PubMed [citation]

PMID:: 8187067

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697484.1

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

Description

Variant summary: This c.192delC variant causes a frameshift, which alters the proteins amino acid sequence beginning at position 65 and leads to a premature termination codon one amino acid downstream. It is predicted to cause a truncated or absent protein product. Mutation taster predicts this variant to be disease-causing. The variant was not observed in the large and broad cohorts of the ExAC project or ESP. The variant of interest has been detected in RCC tumor samples (Shuin_1994 and Suzuki_1997). Truncations downstream of this position have been classified as disease variants by our laboratory (Such as c.214delT and C.230delG). One clinical lab (via ClinVar) classified this variant as pathogenic. Considering all, this variant has been classified as Likely Pathogenic until additional information becomes available.

#	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: Dec 24, 2023

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