NM_000551.4(VHL):c.250G>A (p.Val84Met) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 16, 2022
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:: RCV000492467.5

Allele description [Variation Report for NM_000551.4(VHL):c.250G>A (p.Val84Met)]

NM_000551.4(VHL):c.250G>A (p.Val84Met)

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.250G>A (p.Val84Met)

HGVS:

NC_000003.12:g.10142097G>A
NG_008212.3:g.5463G>A
NM_000551.4:c.250G>AMANE SELECT
NM_001354723.2:c.250G>A
NM_198156.3:c.250G>A
NP_000542.1:p.Val84Met
NP_000542.1:p.Val84Met
NP_001341652.1:p.Val84Met
NP_937799.1:p.Val84Met
LRG_322t1:c.250G>A
LRG_322:g.5463G>A
LRG_322p1:p.Val84Met
NC_000003.11:g.10183781G>A
NM_000551.3:c.250G>A

Protein change:

V84M

Links:

dbSNP: rs5030827

NCBI 1000 Genomes Browser:

rs5030827

Molecular consequence:

NM_000551.4:c.250G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354723.2:c.250G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.250G>A - 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
SCV000580992	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Dec 16, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17688370, 17906660, 20233476, 22438210, 27311873 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000580992

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Dec 16, 2022)

germline

clinical testing

PubMed (5)
[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

Germline VHL gene mutations in three Serbian families with von Hippel-Lindau disease.

Stanojevic BR, Lohse P, Neskovic GG, Damjanovic SM, Novkovic TB, Jovanovic-Cupic SP, Dimitrijević BB.

Neoplasma. 2007;54(5):402-6.

PubMed [citation]

PMID:: 17688370

Nuclear E-cadherin and VHL immunoreactivity are prognostic indicators of clear-cell renal cell carcinoma.

Gervais ML, Henry PC, Saravanan A, Burry TN, Gallie BL, Jewett MA, Hill RP, Evans AJ, Ohh M.

Lab Invest. 2007 Dec;87(12):1252-64. Epub 2007 Oct 1.

PubMed [citation]

PMID:: 17906660

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000580992.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The p.V84M variant (also known as c.250G>A), located in coding exon 1 of the VHL gene, results from a G to A substitution at nucleotide position 250. The valine at codon 84 is replaced by methionine, an amino acid with highly similar properties. This alteration has been reported in an individual affected with bilateral pheochromocytoma diagnosed at ages 1 year and 4 years; of note, this individual's father was also diagnosed with pheochromocytoma at age 40; however, genetic testing was not performed on the father (Stanojevic BR et al. Neoplasma. 2007;54:402-6). It was also identified in a patient diagnosed with a pheochromocytoma at age 8, with recurrence of disease at age 26 (Eisenhofer G et al. Horm. Metab. Res. 2012 May;44(5):343-8). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	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: Oct 8, 2024

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