For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro86 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7728151, 9829911, 11257211, 17024664, 19408298). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt VHL protein function. ClinVar contains an entry for this variant (Variation ID: 178692). This variant is also known as 469C>T, Pro157Ser. This missense change has been observed in individuals with von Hippel-Lindau syndrome (PMID: 8634692, 9829912, 19464396, 27057652, 27527340). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 86 of the VHL protein (p.Pro86Ser).
ClinVar Genomic variation as it relates to human health
NM_000551.4(VHL):c.256C>T (p.Pro86Ser)
Germline
Classification
Help
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.
(6)
Help
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/Likely pathogenic
6
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.256C>T (p.Pro86Ser)
Variation ID: 178692 Accession: VCV000178692.20
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 3p25.3 3: 10142103 (GRCh38) [ NCBI UCSC ] 3: 10183787 (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 Mar 9, 2016 May 1, 2024 Apr 6, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000551.4:c.256C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000542.1:p.Pro86Ser missense NM_001354723.2:c.256C>T NP_001341652.1:p.Pro86Ser missense NM_198156.3:c.256C>T NP_937799.1:p.Pro86Ser missense NC_000003.12:g.10142103C>T NC_000003.11:g.10183787C>T NG_008212.3:g.5469C>T LRG_322:g.5469C>T LRG_322t1:c.256C>T LRG_322p1:p.Pro86Ser P40337:p.Pro86Ser - Protein change
- P86S
- Other names
- -
- Canonical SPDI
- NC_000003.12:10142102:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe 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.
- -
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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 |
832 | 2004 | |
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. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Jan 29, 2016 | RCV000155449.6 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Apr 6, 2023 | RCV000492763.4 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Nov 3, 2022 | RCV000413630.3 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jun 22, 2022 | RCV001059327.8 |
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
(Jun 22, 2022)
|
criteria provided, single submitter
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: SCV001223949.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro86 amino acid residue in VHL. Other variant(s) that disrupt this … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro86 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7728151, 9829911, 11257211, 17024664, 19408298). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt VHL protein function. ClinVar contains an entry for this variant (Variation ID: 178692). This variant is also known as 469C>T, Pro157Ser. This missense change has been observed in individuals with von Hippel-Lindau syndrome (PMID: 8634692, 9829912, 19464396, 27057652, 27527340). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 86 of the VHL protein (p.Pro86Ser). (less)
|
|
|
Pathogenic
(Jan 29, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Von Hippel-Lindau syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697490.1
First in ClinVar: Mar 09, 2016 Last updated: Mar 09, 2016 |
Comment:
Variant summary: This c.256C>T variant affects a conserved nucleotide, resulting in amino acid change from Pro to Ser in HIFalfa domain of VHL protein. 5/5 … (more)
Variant summary: This c.256C>T variant affects a conserved nucleotide, resulting in amino acid change from Pro to Ser in HIFalfa domain of VHL protein. 5/5 in-silico tools predict this variant to be damaging. The variant is absent from the large, broad ExAC control population. In literature, this variant has been reported multiple independent patients with Von Hippel-Lindau disease or related cancers, and has been shown to segregate with disease in at least one family. Other missense changes at this codon are also reported in association VHL disease, namely p.P86R, p.P86L and p.P86A, suggesting that this codon is likely to be a mutational hot-spot. One clinical lab (via ClinVar) and one reputable database classify this variant as pathogenic/likley pathogenic. Taken together, this variant has been classified as a Pathogenic. (less)
|
|
|
Likely pathogenic
(Feb 19, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
Von Hippel-Lindau syndrome
(Autosomal dominant inheritance)
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000205140.5
First in ClinVar: Jan 31, 2015 Last updated: May 03, 2018 |
Comment:
The Pro86Ser variant in VHL has been reported in 12 individuals with clinical fe atures of Von Hippel-Lindau syndrome, was absent from 276 control chromosomes, … (more)
The Pro86Ser variant in VHL has been reported in 12 individuals with clinical fe atures of Von Hippel-Lindau syndrome, was absent from 276 control chromosomes, a nd segregated with disease in four affected family members across three families (Whaley 1994, Kondo 1995, Olschwang 1998, Dollfus 2002, Elii 2006, Ong 2007, Co rcos 2008, Ciotti 2009, Wu 2012). Computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for o r against an impact to the protein, however, proline (Pro) at position 86 is hig hly conserved across evolutionarily distant species, suggesting that a change to this position may not be tolerated. In addition, other variants at this positio n (Pro86Ala, Pro86Leu, Pro86Arg, and Pro86His) have been identified in patients with the clinical features of Von Hippel-Lindau syndrome (HGMD database, UMD dat abase). In summary, this variant is likely to be pathogenic, though additional s tudies are required to fully establish its clinical significance. (less)
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Nov 03, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000490877.4
First in ClinVar: Jan 09, 2017 Last updated: Mar 04, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as c.469C>T, p.P157S, p.P127S; This variant is associated with the following publications: (PMID: 25562111, 7977367, 23660872, 18836774, 8956040, 9829912, 15300849, 8634692, 16952288, 27057652, 22357542, 20151405, 17024664, 10761708, 16506495, 19464396, 19215943, 18580449, 27527340, 33774214, 34926252, Al-Hadlaq[article]2022) (less)
|
|
|
Pathogenic
(Apr 06, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000580953.7
First in ClinVar: Jul 01, 2017 Last updated: May 01, 2024 |
Comment:
The p.P86S pathogenic mutation (also known as c.256C>T), located in coding exon 1 of the VHL gene, results from a C to T substitution at … (more)
The p.P86S pathogenic mutation (also known as c.256C>T), located in coding exon 1 of the VHL gene, results from a C to T substitution at nucleotide position 256. The proline at codon 86 is replaced by serine, an amino acid with similar properties. This mutation has been detected in multiple individuals meeting clinical criteria for Von Hippel-Lindau (VHL) disease with symptoms including retinal angiomas, cerebellar hemangioblastomas, pheochromocytomas, renal cell carcinoma, and pancreatic cysts and tumors (Kondo K et. al. Hum. Mol. Genet. 1995 Dec;4:2233-7; Ong KR, et al. Hum. Mutat. 2007 Feb;28:143-9; Whaley JM et al. Am. J. Hum. Genet. 1994 Dec;55:1092-102; Ciotti P et al. Eur J Med Genet. 2009 May;52:311-4; Dollfus H et al. Invest. Ophthalmol. Vis. Sci. 2002 Sep;43:3067-74; Elli L et al. Am. J. Gastroenterol. 2006 Nov;101:2655-8; Wu P et al. J. Hum. Genet. 2012 Apr;57:238-43; Rothberg PG et al. Mol. Diagn. 2001 Mar;6:49-54; Park TY et al. Scand. J. Gastroenterol. 2015 Mar;50:360-7; Olschwang S et al. Hum. Mutat. 1998;12:424-30; Gallou C et al. Hum. Mutat. 2004 Sep;24:215-24; Corcos O et al. Pancreas. 2008 Jul;37:85-93. Several other alterations at the same codon (p.P86A, p.P86L, and p.P86R) have been reported in individuals with VHL (Nordstrom-O'Brien M et al. Hum. Mutat. 2010 May;31:521-37). In addition, based on both internal structural analysis and published structural analysis, this alteration is anticipated to result in a significant decrease in structural stability (Van Molle I et al. Chem. Biol. 2012 Oct;19:1300-12; Yuan P et al. Cancer Biol. Ther. 2016 Jun;17:599-603). Of note, this mutation is also designated as p.P157S (c.469C>T) in published literature. Based on the supporting evidence, 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: SCV000264684.1
First in ClinVar: Mar 09, 2016 Last updated: Mar 09, 2016 |
Number of individuals with the variant: 14
|
Comment:
Comment:
Variant summary: This c.256C>T variant affects a conserved nucleotide, resulting in amino acid change from Pro to Ser in HIFalfa domain of VHL protein. 5/5 in-silico tools predict this variant to be damaging. The variant is absent from the large, broad ExAC control population. In literature, this variant has been reported multiple independent patients with Von Hippel-Lindau disease or related cancers, and has been shown to segregate with disease in at least one family. Other missense changes at this codon are also reported in association VHL disease, namely p.P86R, p.P86L and p.P86A, suggesting that this codon is likely to be a mutational hot-spot. One clinical lab (via ClinVar) and one reputable database classify this variant as pathogenic/likley pathogenic. Taken together, this variant has been classified as a Pathogenic.
Comment:
The Pro86Ser variant in VHL has been reported in 12 individuals with clinical fe atures of Von Hippel-Lindau syndrome, was absent from 276 control chromosomes, a nd segregated with disease in four affected family members across three families (Whaley 1994, Kondo 1995, Olschwang 1998, Dollfus 2002, Elii 2006, Ong 2007, Co rcos 2008, Ciotti 2009, Wu 2012). Computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for o r against an impact to the protein, however, proline (Pro) at position 86 is hig hly conserved across evolutionarily distant species, suggesting that a change to this position may not be tolerated. In addition, other variants at this positio n (Pro86Ala, Pro86Leu, Pro86Arg, and Pro86His) have been identified in patients with the clinical features of Von Hippel-Lindau syndrome (HGMD database, UMD dat abase). In summary, this variant is likely to be pathogenic, though additional s tudies are required to fully establish its clinical significance.
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as c.469C>T, p.P157S, p.P127S; This variant is associated with the following publications: (PMID: 25562111, 7977367, 23660872, 18836774, 8956040, 9829912, 15300849, 8634692, 16952288, 27057652, 22357542, 20151405, 17024664, 10761708, 16506495, 19464396, 19215943, 18580449, 27527340, 33774214, 34926252, Al-Hadlaq[article]2022)
Comment:
The p.P86S pathogenic mutation (also known as c.256C>T), located in coding exon 1 of the VHL gene, results from a C to T substitution at nucleotide position 256. The proline at codon 86 is replaced by serine, an amino acid with similar properties. This mutation has been detected in multiple individuals meeting clinical criteria for Von Hippel-Lindau (VHL) disease with symptoms including retinal angiomas, cerebellar hemangioblastomas, pheochromocytomas, renal cell carcinoma, and pancreatic cysts and tumors (Kondo K et. al. Hum. Mol. Genet. 1995 Dec;4:2233-7; Ong KR, et al. Hum. Mutat. 2007 Feb;28:143-9; Whaley JM et al. Am. J. Hum. Genet. 1994 Dec;55:1092-102; Ciotti P et al. Eur J Med Genet. 2009 May;52:311-4; Dollfus H et al. Invest. Ophthalmol. Vis. Sci. 2002 Sep;43:3067-74; Elli L et al. Am. J. Gastroenterol. 2006 Nov;101:2655-8; Wu P et al. J. Hum. Genet. 2012 Apr;57:238-43; Rothberg PG et al. Mol. Diagn. 2001 Mar;6:49-54; Park TY et al. Scand. J. Gastroenterol. 2015 Mar;50:360-7; Olschwang S et al. Hum. Mutat. 1998;12:424-30; Gallou C et al. Hum. Mutat. 2004 Sep;24:215-24; Corcos O et al. Pancreas. 2008 Jul;37:85-93. Several other alterations at the same codon (p.P86A, p.P86L, and p.P86R) have been reported in individuals with VHL (Nordstrom-O'Brien M et al. Hum. Mutat. 2010 May;31:521-37). In addition, based on both internal structural analysis and published structural analysis, this alteration is anticipated to result in a significant decrease in structural stability (Van Molle I et al. Chem. Biol. 2012 Oct;19:1300-12; Yuan P et al. Cancer Biol. Ther. 2016 Jun;17:599-603). Of note, this mutation is also designated as p.P157S (c.469C>T) in published literature. Based on the supporting evidence, 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:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro86 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7728151, 9829911, 11257211, 17024664, 19408298). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt VHL protein function. ClinVar contains an entry for this variant (Variation ID: 178692). This variant is also known as 469C>T, Pro157Ser. This missense change has been observed in individuals with von Hippel-Lindau syndrome (PMID: 8634692, 9829912, 19464396, 27057652, 27527340). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 86 of the VHL protein (p.Pro86Ser).
Comment:
Variant summary: This c.256C>T variant affects a conserved nucleotide, resulting in amino acid change from Pro to Ser in HIFalfa domain of VHL protein. 5/5 in-silico tools predict this variant to be damaging. The variant is absent from the large, broad ExAC control population. In literature, this variant has been reported multiple independent patients with Von Hippel-Lindau disease or related cancers, and has been shown to segregate with disease in at least one family. Other missense changes at this codon are also reported in association VHL disease, namely p.P86R, p.P86L and p.P86A, suggesting that this codon is likely to be a mutational hot-spot. One clinical lab (via ClinVar) and one reputable database classify this variant as pathogenic/likley pathogenic. Taken together, this variant has been classified as a Pathogenic.
Comment:
The Pro86Ser variant in VHL has been reported in 12 individuals with clinical fe atures of Von Hippel-Lindau syndrome, was absent from 276 control chromosomes, a nd segregated with disease in four affected family members across three families (Whaley 1994, Kondo 1995, Olschwang 1998, Dollfus 2002, Elii 2006, Ong 2007, Co rcos 2008, Ciotti 2009, Wu 2012). Computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for o r against an impact to the protein, however, proline (Pro) at position 86 is hig hly conserved across evolutionarily distant species, suggesting that a change to this position may not be tolerated. In addition, other variants at this positio n (Pro86Ala, Pro86Leu, Pro86Arg, and Pro86His) have been identified in patients with the clinical features of Von Hippel-Lindau syndrome (HGMD database, UMD dat abase). In summary, this variant is likely to be pathogenic, though additional s tudies are required to fully establish its clinical significance.
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as c.469C>T, p.P157S, p.P127S; This variant is associated with the following publications: (PMID: 25562111, 7977367, 23660872, 18836774, 8956040, 9829912, 15300849, 8634692, 16952288, 27057652, 22357542, 20151405, 17024664, 10761708, 16506495, 19464396, 19215943, 18580449, 27527340, 33774214, 34926252, Al-Hadlaq[article]2022)
Comment:
The p.P86S pathogenic mutation (also known as c.256C>T), located in coding exon 1 of the VHL gene, results from a C to T substitution at nucleotide position 256. The proline at codon 86 is replaced by serine, an amino acid with similar properties. This mutation has been detected in multiple individuals meeting clinical criteria for Von Hippel-Lindau (VHL) disease with symptoms including retinal angiomas, cerebellar hemangioblastomas, pheochromocytomas, renal cell carcinoma, and pancreatic cysts and tumors (Kondo K et. al. Hum. Mol. Genet. 1995 Dec;4:2233-7; Ong KR, et al. Hum. Mutat. 2007 Feb;28:143-9; Whaley JM et al. Am. J. Hum. Genet. 1994 Dec;55:1092-102; Ciotti P et al. Eur J Med Genet. 2009 May;52:311-4; Dollfus H et al. Invest. Ophthalmol. Vis. Sci. 2002 Sep;43:3067-74; Elli L et al. Am. J. Gastroenterol. 2006 Nov;101:2655-8; Wu P et al. J. Hum. Genet. 2012 Apr;57:238-43; Rothberg PG et al. Mol. Diagn. 2001 Mar;6:49-54; Park TY et al. Scand. J. Gastroenterol. 2015 Mar;50:360-7; Olschwang S et al. Hum. Mutat. 1998;12:424-30; Gallou C et al. Hum. Mutat. 2004 Sep;24:215-24; Corcos O et al. Pancreas. 2008 Jul;37:85-93. Several other alterations at the same codon (p.P86A, p.P86L, and p.P86R) have been reported in individuals with VHL (Nordstrom-O'Brien M et al. Hum. Mutat. 2010 May;31:521-37). In addition, based on both internal structural analysis and published structural analysis, this alteration is anticipated to result in a significant decrease in structural stability (Van Molle I et al. Chem. Biol. 2012 Oct;19:1300-12; Yuan P et al. Cancer Biol. Ther. 2016 Jun;17:599-603). Of note, this mutation is also designated as p.P157S (c.469C>T) in published literature. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Clinical and molecular characteristics of East Asian patients with von Hippel-Lindau syndrome. | Wong M | Chinese journal of cancer | 2016 | PMID: 27527340 |
| Germline mutations in the VHL gene associated with 3 different renal lesions in a Chinese von Hippel-Lindau disease family. | Yuan P | Cancer biology & therapy | 2016 | PMID: 27057652 |
| Clinical features of pancreatic involvement in von Hippel-Lindau disease: a retrospective study of 55 cases in a single center. | Park TY | Scandinavian journal of gastroenterology | 2015 | PMID: 25562111 |
| Integrative analysis of miRNA and mRNA expression profiles in pheochromocytoma and paraganglioma identifies genotype-specific markers and potentially regulated pathways. | de Cubas AA | Endocrine-related cancer | 2013 | PMID: 23660872 |
| Family history of von Hippel-Lindau disease was uncommon in Chinese patients: suggesting the higher frequency of de novo mutations in VHL gene in these patients. | Wu P | Journal of human genetics | 2012 | PMID: 22357542 |
| Genetic analysis of von Hippel-Lindau disease. | Nordstrom-O'Brien M | Human mutation | 2010 | PMID: 20151405 |
| Germline mutations in the von Hippel-Lindau gene in Italian patients. | Ciotti P | European journal of medical genetics | 2009 | PMID: 19464396 |
| Structural bioinformatics mutation analysis reveals genotype-phenotype correlations in von Hippel-Lindau disease and suggests molecular mechanisms of tumorigenesis. | Forman JR | Proteins | 2009 | PMID: 19408298 |
| Endocrine pancreatic tumors in von Hippel-Lindau disease: clinical, histological, and genetic features. | Corcos O | Pancreas | 2008 | PMID: 18580449 |
| Genotype-phenotype correlations in von Hippel-Lindau disease. | Ong KR | Human mutation | 2007 | PMID: 17024664 |
| Pancreatic involvement in von Hippel-Lindau disease: report of two cases and review of the literature. | Elli L | The American journal of gastroenterology | 2006 | PMID: 16952288 |
| Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions. | Gallou C | Human mutation | 2004 | PMID: 15300849 |
| Retinal hemangioblastoma in von Hippel-Lindau disease: a clinical and molecular study. | Dollfus H | Investigative ophthalmology & visual science | 2002 | PMID: 12202531 |
| Is the P25L a "real" VHL mutation? | Rothberg PG | Molecular diagnosis : a journal devoted to the understanding of human disease through the clinical application of molecular biology | 2001 | PMID: 11257211 |
| Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein. | Cockman ME | The Journal of biological chemistry | 2000 | PMID: 10823831 |
| 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 in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan. | Zbar B | Human mutation | 1996 | PMID: 8956040 |
| Germline mutations in the von Hippel-Lindau disease (VHL) gene in Japanese VHL. Clinical Research Group for VHL in Japan. | - | Human molecular genetics | 1995 | PMID: 8634692 |
| Germline mutations in the von Hippel-Lindau disease tumor suppressor gene: correlations with phenotype. | Chen F | Human mutation | 1995 | PMID: 7728151 |
| Cellular proteins that bind the von Hippel-Lindau disease gene product: mapping of binding domains and the effect of missense mutations. | Kishida T | Cancer research | 1995 | PMID: 7553625 |
| Germ-line mutations in the von Hippel-Lindau tumor-suppressor gene are similar to somatic von Hippel-Lindau aberrations in sporadic renal cell carcinoma. | Whaley JM | American journal of human genetics | 1994 | PMID: 7977367 |
| click to load more click to collapse | ||||
Text-mined citations for rs398123481 ...
HelpThese 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 Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.