NM_000551.4(VHL):c.191G>C (p.Arg64Pro) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 17, 2019
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:: RCV000132356.5

Allele description [Variation Report for NM_000551.4(VHL):c.191G>C (p.Arg64Pro)]

NM_000551.4(VHL):c.191G>C (p.Arg64Pro)

Gene:

VHL:von Hippel-Lindau tumor suppressor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_000551.4(VHL):c.191G>C (p.Arg64Pro)

Other names:

NM_000551.4(VHL):c.191G>C

HGVS:

NC_000003.12:g.10142038G>C
NG_008212.3:g.5404G>C
NM_000551.4:c.191G>CMANE SELECT
NM_001354723.2:c.191G>C
NM_198156.3:c.191G>C
NP_000542.1:p.Arg64Pro
NP_000542.1:p.Arg64Pro
NP_001341652.1:p.Arg64Pro
NP_937799.1:p.Arg64Pro
LRG_322t1:c.191G>C
LRG_322:g.5404G>C
LRG_322p1:p.Arg64Pro
NC_000003.11:g.10183722G>C
NM_000551.3:c.191G>C
P40337:p.Arg64Pro
p.R64P
p.[Arg64Pro]

Protein change:

R64P; ARG64PRO

Links:

UniProtKB: P40337#VAR_034988; OMIM: 608537.0015; dbSNP: rs104893826

NCBI 1000 Genomes Browser:

rs104893826

Molecular consequence:

NM_000551.4:c.191G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354723.2:c.191G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.191G>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000187445	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 17, 2019)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 11331612, 19336503, 19808854, 21463266, 24555745, 9663592 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000187445

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 17, 2019)

germline

clinical testing

PubMed (6)
[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

von Hippel-Lindau protein mutants linked to type 2C VHL disease preserve the ability to downregulate HIF.

Hoffman MA, Ohh M, Yang H, Klco JM, Ivan M, Kaelin WG Jr.

Hum Mol Genet. 2001 May 1;10(10):1019-27.

PubMed [citation]

PMID:: 11331612

Head and neck paragangliomas in von Hippel-Lindau disease and multiple endocrine neoplasia type 2.

Boedeker CC, Erlic Z, Richard S, Kontny U, Gimenez-Roqueplo AP, Cascon A, Robledo M, de Campos JM, van Nederveen FH, de Krijger RR, Burnichon N, Gaal J, Walter MA, Reschke K, Wiech T, Weber J, Rückauer K, Plouin PF, Darrouzet V, Giraud S, Eng C, Neumann HP.

J Clin Endocrinol Metab. 2009 Jun;94(6):1938-44. doi: 10.1210/jc.2009-0354. Epub 2009 Mar 31. Review.

PubMed [citation]

PMID:: 19336503
PMCID:: PMC2690424

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV000187445.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The p.R64P pathogenic mutation (also known as c.191G>C), located in coding exon 1 of the VHL gene, results from a G to C substitution at nucleotide position 191. The arginine at codon 64 is replaced by proline, an amino acid with dissimilar properties. This mutation has been reported in multiple individuals and/or families diagnosed with VHL (van der Harst E et al. Int J Cancer. 1998 Jul 29;77(3):337-40; Hoffman MA et al. Hum. Mol. Genet. 2001 May;10:1019-27; Hes FJ et al. Clin Genet. 2007 Aug;72(2):122-9; Boedeker CC et al. J. Clin. Endocrinol. Metab. 2009 Jun;94:1938-44; Wittström E et al. Ophthalmic Genet. 2014 Jun;35:91-106). In addition, a 23-year-old female diagnosed with a neck PGL who had a family history of PCCs and clear cell renal cell carcinoma was found to carry this alteration, and her tumor showed LOH for the wild-type allele (Gaal J et al. J Clin Endocrinol Metab. 2009 Nov;94(11):4367-71). Based on the supporting evidence, 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: Sep 29, 2024

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