VCV000002217.34 - ClinVar

NM_000551.4(VHL):c.481C>T (p.Arg161Ter)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(13)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000551.4(VHL):c.481C>T (p.Arg161Ter)

Variation ID: 2217 Accession: VCV000002217.34

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3p25.3 3: 10149804 (GRCh38) [ NCBI UCSC ] 3: 10191488 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 4, 2013	May 1, 2024	Dec 29, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000551.4:c.481C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000542.1:p.Arg161Ter	nonsense
NM_001354723.2:c.*35C>T		3 prime UTR
NM_198156.3:c.358C>T	NP_937799.1:p.Arg120Ter	nonsense
NC_000003.12:g.10149804C>T
NC_000003.11:g.10191488C>T
NG_008212.3:g.13170C>T
NG_046756.1:g.7566C>T
LRG_322:g.13170C>T
LRG_322t1:c.481C>T	LRG_322p1:p.Arg161Ter

... more HGVS ... less HGVS

Protein change

R161*, R120*

Other names

p.R161*:CGA>TGA

Canonical SPDI

NC_000003.12:10149803:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.00000

Links

ClinGen: CA020408 OMIM: 608537.0006 dbSNP: rs5030818 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
VHL		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	834	2006
LOC107303340	-	-	-	GRCh38	-	1117

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Von Hippel-Lindau syndrome	Pathogenic (5)	criteria provided, multiple submitters, no conflicts	Jul 22, 2019	RCV000002301.21
not provided	Pathogenic (4)	criteria provided, multiple submitters, no conflicts	Feb 7, 2023	RCV000161091.26
Hereditary cancer-predisposing syndrome	Pathogenic (1)	criteria provided, single submitter	Apr 17, 2023	RCV000492225.12
Papillary renal cell carcinoma type 1	Likely pathogenic (1)	no assertion criteria provided	Jul 14, 2015	RCV000437445.8
Chuvash polycythemia Von Hippel-Lindau syndrome	Pathogenic (1)	criteria provided, single submitter	Dec 29, 2023	RCV000791367.14
Familial infantile myasthenia	Pathogenic (1)	no assertion criteria provided	Dec 27, 2017	RCV001280922.8

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (May 28, 2014)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000228904.5 First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=VHL Number of individuals with the variant: 3 Sex: mixed
Pathogenic (Jul 22, 2019)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Von Hippel-Lindau syndrome Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000053265.2 First in ClinVar: Apr 04, 2013 Last updated: Jun 22, 2020	Publications: PubMed (7) PubMed: 12114495‚ 15300849‚ 9452032‚ 7987327‚ 8730290‚ 14722919‚ 8956040 Comment: Variant summary: VHL c.481C>T (p.Arg161X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more) Variant summary: VHL c.481C>T (p.Arg161X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251440 control chromosomes. c.481C>T has been extensively reported in the literature spanning over two decades to co-segregate with disease among multiple affected individuals from families with Von Hippel-Lindau Syndrome (example, Loeb_1994, Zbar_1996, Maher_1996, Li_1998, Cybulski_2002, Ruiz-Llorente_2004, Gallou_2004). These data indicate that the variant is very likely to be associated with disease. No experimental evidence demonstrating an impact on protein function was ascertained during this review. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
Pathogenic (Nov 03, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden Accession: SCV002011309.3 First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023
Pathogenic (Apr 16, 2018)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process) Method: clinical testing	Not Provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000884875.1 First in ClinVar: Dec 15, 2018 Last updated: Dec 15, 2018	Comment: The VHL c.481C>T; p.Arg161Ter variant (rs5030818), also known as c.694C>T for traditional nomenclature, is reported multiple times in the literature in association with von Hippel-Lindau … (more) The VHL c.481C>T; p.Arg161Ter variant (rs5030818), also known as c.694C>T for traditional nomenclature, is reported multiple times in the literature in association with von Hippel-Lindau disease (see Cybulski 2002, Glavac 1996, Nordstrom-O'Brien 2010, Stolle 1998, Zbar 1996). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 2217), and it is absent from the general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database). This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-medicated decay. Based on available information, this variant is considered to be pathogenic. REFERENCES Cybulski C et al. Germline mutations in the von Hippel-Lindau (VHL) gene in patients from Poland: disease presentation in patients with deletions of the entire VHL gene. J Med Genet. 2002 Jul;39(7):E38. Glavac D et al. Mutations in the VHL tumor suppressor gene and associated lesions in families with von Hippel-Lindau disease from central Europe. Hum Genet. 1996 Sep;98(3):271-80. Nordstrom-O'Brien M et al. Genetic analysis of von Hippel-Lindau disease. Hum Mutat. 2010 May;31(5):521-37. Stolle C et al. Improved detection of germline mutations in the von Hippel-Lindau disease tumor suppressor gene. Hum Mutat. 1998;12(6):417-23. Zbar B et al. Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan. Hum Mutat. 1996;8(4):348-57. (less)
Pathogenic (May 04, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Von Hippel-Lindau syndrome Affected status: unknown Allele origin: germline	Clinical Genomics Labs, University Health Network Accession: SCV001950138.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Pathogenic (Feb 07, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000211826.13 First in ClinVar: Feb 24, 2015 Last updated: Feb 18, 2023	Comment: Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 53 amino acids are lost, and other loss-of-function variants have been … (more) Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 53 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21362373, 26514359, 23070752, 9829911, 12114495, 10408776, 21972040, 8956040, 25867206, 27527340, 7987306, 25720320, 24581539, 18446368, 9829912, 19574279, 11409863, 19996202, 28630796, 14987375, 9681856, 17661816, 11309459, 20064270, 16572651, 28849724, 7987327, 28469506, 30787465, 33720516, 20233476, 32782288, 32974018) (less)
Pathogenic (Dec 29, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Von Hippel-Lindau syndrome Chuvash polycythemia Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000553380.8 First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024	Publications: PubMed (21) PubMed: 7987306‚ 8956040‚ 9452032‚ 9829911‚ 9829912‚ 10567493‚ 12114495‚ 14722919‚ 15300849‚ 18446368‚ 19270817‚ 21362373‚ 24206762‚ 24301059‚ 25867206‚ 7728151‚ 12000816‚ 14767570‚ 20120764‚ 23842656‚ 24707167 Comment: This sequence change creates a premature translational stop signal (p.Arg161) in the VHL gene. While this is not anticipated to result in nonsense mediated decay, … (more) This sequence change creates a premature translational stop signal (p.Arg161) in the VHL gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 53 amino acid(s) of the VHL protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with von Hippel-Lindau syndrome (PMID: 7987306, 8956040, 9452032, 9829911, 9829912, 10567493, 12114495, 14722919, 15300849, 18446368, 19270817, 21362373, 24206762, 24301059, 25867206). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is also known as c.694C>T. ClinVar contains an entry for this variant (Variation ID: 2217). This variant disrupts the p.Arg161 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7728151, 9829911, 12000816, 14767570, 15300849, 20120764, 21362373, 23842656, 24707167). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Apr 17, 2023)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000580965.7 First in ClinVar: Jul 01, 2017 Last updated: May 01, 2024	Publications: PubMed (6) PubMed: 25720320‚ 27527340‚ 27617348‚ 7987327‚ 8730290‚ 8956040 Comment: The p.R161* pathogenic mutation (also known as c.481C>T) located in coding exon 3 of the VHL gene, results from a C to T substitution at … (more) The p.R161* pathogenic mutation (also known as c.481C>T) located in coding exon 3 of the VHL gene, results from a C to T substitution at nucleotide position 481. This changes the amino acid from an arginine to a stop codon within coding exon 3. This mutation has been reported in several individuals with personal and family histories of Von Hippel-Lindau (VHL) syndrome (Cho HJ et al. J Korean Med Sci. 2009 Feb;24:77-83; Siu WK et al. Chin. Med. J. 2011 Jan;124:237-41; Zbar B et al. Hum. Mutat. 1996;8:348-57; Papathomas TG et al. Mod. Pathol. 2015 Jun;28:807-21; Wong M et al. Chin J Cancer. 2016 Aug;35:79; Sriphrapradang C et al. Clin Med Insights Endocrinol Diabetes. 2017 Apr;10:1179551417705122). A 48 year old male with bilateral renal clear cell carcinoma and a clinical diagnosis of VHL was found to be a mosaic carrier of this pathogenic mutation (Coppin L et al. Eur. J. Hum. Genet. 2014 Sept;22:1149-52). 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. (less)
Pathogenic (Feb 26, 2016)	no assertion criteria provided Method: clinical testing	Von Hippel-Lindau syndrome Affected status: yes Allele origin: germline	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia Accession: SCV000264756.1 First in ClinVar: Mar 08, 2016 Last updated: Mar 08, 2016	Number of individuals with the variant: 32
Pathogenic (Oct 16, 2007)	no assertion criteria provided Method: clinical testing	Von Hippel-Lindau syndrome Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000060202.5 First in ClinVar: May 03, 2013 Last updated: Aug 14, 2019	Publications: PubMed (2) PubMed: 8956040‚ 8730290 Number of individuals with the variant: 1
Pathogenic (Dec 01, 1995)	no assertion criteria provided Method: literature only	VON HIPPEL-LINDAU SYNDROME Affected status: not provided Allele origin: unknown	OMIM Accession: SCV000022459.2 First in ClinVar: Apr 04, 2013 Last updated: Mar 09, 2020	Publications: PubMed (3) PubMed: 7784063‚ 7987327‚ 8522307 Comment on evidence: Following the revised codon numbering system of Kuzmin et al. (1995), the ARG232TER mutation has been renumbered as ARG161TER (R161X). In a patient with von … (more) Following the revised codon numbering system of Kuzmin et al. (1995), the ARG232TER mutation has been renumbered as ARG161TER (R161X). In a patient with von Hippel-Lindau syndrome (VHLS; 193300), Loeb et al. (1994) identified a 694C-T transition in exon 3 of the VHL gene, resulting in an amber stop codon arg232-to-ter (R232X). Gilcrease et al. (1995) found the identical 694C-T transition as a somatic mutation in a clear cell papillary cystadenoma of the epididymis in a patient who showed no evidence of von Hippel-Lindau syndrome and in whom somatic cells did not contain this mutation. (less)
Likely pathogenic (Jul 14, 2015)	no assertion criteria provided Method: literature only	Renal cell carcinoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000505322.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 25157968 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000256474:c.481C>T
Pathogenic (Dec 27, 2017)	no assertion criteria provided Method: clinical testing	Familial infantile myasthenia (Autosomal recessive inheritance) Affected status: yes Allele origin: tested-inconclusive	Neuromuscular Department, Shariati Hospital, Tehran University of Medical Sciences Accession: SCV001450647.1 First in ClinVar: Jan 09, 2021 Last updated: Jan 09, 2021	Number of individuals with the variant: 1 Age: 30-39 years Sex: male Ethnicity/Population group: Iranian Geographic origin: Iran Comment on evidence: A 31-year-old man with bilateral ptosis, limited eye movement, moderate proximal muscle weakness, and facial weakness since childhood.
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Comment:

Variant summary: VHL c.481C>T (p.Arg161X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251440 control chromosomes. c.481C>T has been extensively reported in the literature spanning over two decades to co-segregate with disease among multiple affected individuals from families with Von Hippel-Lindau Syndrome (example, Loeb_1994, Zbar_1996, Maher_1996, Li_1998, Cybulski_2002, Ruiz-Llorente_2004, Gallou_2004). These data indicate that the variant is very likely to be associated with disease. No experimental evidence demonstrating an impact on protein function was ascertained during this review. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

Comment:

The VHL c.481C>T; p.Arg161Ter variant (rs5030818), also known as c.694C>T for traditional nomenclature, is reported multiple times in the literature in association with von Hippel-Lindau disease (see Cybulski 2002, Glavac 1996, Nordstrom-O'Brien 2010, Stolle 1998, Zbar 1996). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 2217), and it is absent from the general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database). This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-medicated decay. Based on available information, this variant is considered to be pathogenic. REFERENCES Cybulski C et al. Germline mutations in the von Hippel-Lindau (VHL) gene in patients from Poland: disease presentation in patients with deletions of the entire VHL gene. J Med Genet. 2002 Jul;39(7):E38. Glavac D et al. Mutations in the VHL tumor suppressor gene and associated lesions in families with von Hippel-Lindau disease from central Europe. Hum Genet. 1996 Sep;98(3):271-80. Nordstrom-O'Brien M et al. Genetic analysis of von Hippel-Lindau disease. Hum Mutat. 2010 May;31(5):521-37. Stolle C et al. Improved detection of germline mutations in the von Hippel-Lindau disease tumor suppressor gene. Hum Mutat. 1998;12(6):417-23. Zbar B et al. Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan. Hum Mutat. 1996;8(4):348-57.

Comment:

Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 53 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21362373, 26514359, 23070752, 9829911, 12114495, 10408776, 21972040, 8956040, 25867206, 27527340, 7987306, 25720320, 24581539, 18446368, 9829912, 19574279, 11409863, 19996202, 28630796, 14987375, 9681856, 17661816, 11309459, 20064270, 16572651, 28849724, 7987327, 28469506, 30787465, 33720516, 20233476, 32782288, 32974018)

Comment:

This sequence change creates a premature translational stop signal (p.Arg161*) in the VHL gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 53 amino acid(s) of the VHL protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with von Hippel-Lindau syndrome (PMID: 7987306, 8956040, 9452032, 9829911, 9829912, 10567493, 12114495, 14722919, 15300849, 18446368, 19270817, 21362373, 24206762, 24301059, 25867206). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is also known as c.694C>T. ClinVar contains an entry for this variant (Variation ID: 2217). This variant disrupts the p.Arg161 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7728151, 9829911, 12000816, 14767570, 15300849, 20120764, 21362373, 23842656, 24707167). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

Comment:

The p.R161* pathogenic mutation (also known as c.481C>T) located in coding exon 3 of the VHL gene, results from a C to T substitution at nucleotide position 481. This changes the amino acid from an arginine to a stop codon within coding exon 3. This mutation has been reported in several individuals with personal and family histories of Von Hippel-Lindau (VHL) syndrome (Cho HJ et al. J Korean Med Sci. 2009 Feb;24:77-83; Siu WK et al. Chin. Med. J. 2011 Jan;124:237-41; Zbar B et al. Hum. Mutat. 1996;8:348-57; Papathomas TG et al. Mod. Pathol. 2015 Jun;28:807-21; Wong M et al. Chin J Cancer. 2016 Aug;35:79; Sriphrapradang C et al. Clin Med Insights Endocrinol Diabetes. 2017 Apr;10:1179551417705122). A 48 year old male with bilateral renal clear cell carcinoma and a clinical diagnosis of VHL was found to be a mosaic carrier of this pathogenic mutation (Coppin L et al. Eur. J. Hum. Genet. 2014 Sept;22:1149-52). 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.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
VHL Germline Mutations in Argentinian Patients with Clinical Diagnoses or Single Typical Manifestations of Type 1 von Hippel-Lindau Disease.	Mathó C	Genetic testing and molecular biomarkers	2016	PMID: 27617348
Clinical and molecular characteristics of East Asian patients with von Hippel-Lindau syndrome.	Wong M	Chinese journal of cancer	2016	PMID: 27527340
Characterization of endolymphatic sac tumors and von Hippel-Lindau disease in the International Endolymphatic Sac Tumor Registry.	Bausch B	Head & neck	2016	PMID: 25867206
SDHB/SDHA immunohistochemistry in pheochromocytomas and paragangliomas: a multicenter interobserver variation analysis using virtual microscopy: a Multinational Study of the European Network for the Study of Adrenal Tumors (ENS@T).	Papathomas TG	Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc	2015	PMID: 25720320
Prospective enterprise-level molecular genotyping of a cohort of cancer patients.	MacConaill LE	The Journal of molecular diagnostics : JMD	2014	PMID: 25157968
Bilateral papillopathy as a presenting sign of pheochromocytoma associated with von Hippel-Lindau disease.	Shah V	Clinical ophthalmology (Auckland, N.Z.)	2014	PMID: 24707167
VHL mosaicism can be detected by clinical next-generation sequencing and is not restricted to patients with a mild phenotype.	Coppin L	European journal of human genetics : EJHG	2014	PMID: 24301059
Persistent exudative retinal detachment after photodynamic therapy and intravitreal bevacizumab injection for multiple retinal capillary hemangiomas in a patient with von Hippel-Lindau disease.	Tsai FY	Journal of the Chinese Medical Association : JCMA	2014	PMID: 24206762
p.N78S and p.R161Q germline mutations of the VHL gene are present in von Hippel-Lindau syndrome in two pedigrees.	Qi XP	Molecular medicine reports	2013	PMID: 23842656
Molecular basis of von Hippel-Lindau syndrome in Chinese patients.	Siu WK	Chinese medical journal	2011	PMID: 21362373
Bilateral pheochromocytoma as first presentation of von Hippel-Lindau disease in a Chinese family.	Tong AL	Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih	2009	PMID: 20120764
Improved detection of germline mutations in Korean VHL patients by multiple ligation-dependent probe amplification analysis.	Cho HJ	Journal of Korean medical science	2009	PMID: 19270817
Germline mutations in the von Hippel-Lindau disease (VHL) gene in mainland Chinese families.	Zhang J	Journal of cancer research and clinical oncology	2008	PMID: 18446368
Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions.	Gallou C	Human mutation	2004	PMID: 15300849
A variety of phenotype with R161Q germline mutation of the von Hippel-Lindau tumor suppressor gene in Japanese kindred.	Iida K	International journal of molecular medicine	2004	PMID: 14767570
Genetic characterization and structural analysis of VHL Spanish families to define genotype-phenotype correlations.	Ruiz-Llorente S	Human mutation	2004	PMID: 14722919
Germline mutations in the von Hippel-Lindau (VHL) gene in patients from Poland: disease presentation in patients with deletions of the entire VHL gene.	Cybulski C	Journal of medical genetics	2002	PMID: 12114495
Germ-line mutations in nonsyndromic pheochromocytoma.	Neumann HP	The New England journal of medicine	2002	PMID: 12000816
The impact of molecular genetic analysis of the VHL gene in patients with haemangioblastomas of the central nervous system.	Gläsker S	Journal of neurology, neurosurgery, and psychiatry	1999	PMID: 10567493
Germline mutation profile of the VHL gene in von Hippel-Lindau disease and in sporadic hemangioblastoma.	Olschwang S	Human mutation	1998	PMID: 9829912
Improved detection of germline mutations in the von Hippel-Lindau disease tumor suppressor gene.	Stolle C	Human mutation	1998	PMID: 9829911
Germline mutations detected in the von Hippel-Lindau disease tumor suppressor gene by Southern blot and direct genomic DNA sequencing.	Li C	Human mutation	1998	PMID: 9452032
Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan.	Zbar B	Human mutation	1996	PMID: 8956040
Phenotypic expression in von Hippel-Lindau disease: correlations with germline VHL gene mutations.	Maher ER	Journal of medical genetics	1996	PMID: 8730290
Somatic von Hippel-Lindau mutation in clear cell papillary cystadenoma of the epididymis.	Gilcrease MZ	Human pathology	1995	PMID: 8522307
Identification of the promoter of the human von Hippel-Lindau disease tumor suppressor gene.	Kuzmin I	Oncogene	1995	PMID: 7784063
Germline mutations in the von Hippel-Lindau disease tumor suppressor gene: correlations with phenotype.	Chen F	Human mutation	1995	PMID: 7728151
A novel mutation in the von Hippel-Lindau gene.	Loeb DB	Human molecular genetics	1994	PMID: 7987327
Identification of intragenic mutations in the von Hippel-Lindau disease tumour suppressor gene and correlation with disease phenotype.	Crossey PA	Human molecular genetics	1994	PMID: 7987306
http://docm.genome.wustl.edu/variants/ENST00000256474:c.481C>T	-	-	-	-
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=VHL	-	-	-	-
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Text-mined citations for rs5030818 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000551.4(VHL):c.481C>T (p.Arg161Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs5030818 ...