NM_000551.4(VHL):c.581T>G (p.Val194Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 28, 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:: RCV000492180.3

Allele description [Variation Report for NM_000551.4(VHL):c.581T>G (p.Val194Gly)]

NM_000551.4(VHL):c.581T>G (p.Val194Gly)

Genes:

LOC107303340:3p25 von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase Alu-mediated recombination region [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.581T>G (p.Val194Gly)

HGVS:

NC_000003.12:g.10149904T>G
NG_008212.3:g.13270T>G
NG_046756.1:g.7666T>G
NM_000551.4:c.581T>GMANE SELECT
NM_001354723.2:c.*135T>G
NM_198156.3:c.458T>G
NP_000542.1:p.Val194Gly
NP_000542.1:p.Val194Gly
NP_937799.1:p.Val153Gly
LRG_322t1:c.581T>G
LRG_322:g.13270T>G
LRG_322p1:p.Val194Gly
NC_000003.11:g.10191588T>G
NM_000551.3:c.581T>G

Protein change:

V153G

Links:

dbSNP: rs1131690963

NCBI 1000 Genomes Browser:

rs1131690963

Molecular consequence:

NM_001354723.2:c.*135T>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000551.4:c.581T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.458T>G - 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
SCV000580988	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jun 28, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000580988

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jun 28, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

In Silico Analysis Identification of a Novel Germ-Line VHL Mutation in a Patient of Malignant Pheochromocytoma.

Kawashima ST, Usui T, Tenjin A, Asai S, Tanaka Y, Hoshikawa M, Shimatsu A, Katabami T.

Endocr Pract. 2014 Jun;20(6):e96-101. doi: 10.4158/EP13403.CR.

PubMed [citation]

PMID:: 24518179

Details of each submission

From Ambry Genetics, SCV000580988.6

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

Description

The p.V194G variant (also known as c.581T>G), located in coding exon 3 of the VHL gene, results from a T to G substitution at nucleotide position 581. The valine at codon 194 is replaced by glycine, an amino acid with dissimilar properties. This alteration was first reported in a 17 year-old female patient presenting with malignant pheochromocytoma. Tissue analyses conducted on three distinct tumors from this patient all demonstrated loss of heterozygosity. This alteration was also detected in this patient's father, who was reported to be unaffected at the time of the study (Kawashima S et al. Endocr Pract. 2014 Jun;20(6):e96-e101). This alteration was found to segregate with disease in a family with clinical history suggestive of VHL (Ambry internal data). This amino acid position is well 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: Sep 29, 2024

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