NM_000551.4(VHL):c.277G>C (p.Gly93Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 19, 2018
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:: RCV002433917.2

Allele description [Variation Report for NM_000551.4(VHL):c.277G>C (p.Gly93Arg)]

NM_000551.4(VHL):c.277G>C (p.Gly93Arg)

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.277G>C (p.Gly93Arg)

HGVS:

NC_000003.12:g.10142124G>C
NG_008212.3:g.5490G>C
NM_000551.4:c.277G>CMANE SELECT
NM_001354723.2:c.277G>C
NM_198156.3:c.277G>C
NP_000542.1:p.Gly93Arg
NP_000542.1:p.Gly93Arg
NP_001341652.1:p.Gly93Arg
NP_937799.1:p.Gly93Arg
LRG_322t1:c.277G>C
LRG_322:g.5490G>C
LRG_322p1:p.Gly93Arg
NC_000003.11:g.10183808G>C
NM_000551.3:c.277G>C
p.[Gly93Arg]

Protein change:

G93R

Links:

dbSNP: rs5030808

NCBI 1000 Genomes Browser:

rs5030808

Molecular consequence:

NM_000551.4:c.277G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354723.2:c.277G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.277G>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
SCV002751678	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Feb 19, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11409863, 23660872 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002751678

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Feb 19, 2018)

germline

clinical testing

PubMed (2)
[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

DHPLC-based germline mutation screening in the analysis of the VHL tumor suppressor gene: usefulness and limitations.

Klein B, Weirich G, Brauch H.

Hum Genet. 2001 May;108(5):376-84.

PubMed [citation]

PMID:: 11409863

Integrative analysis of miRNA and mRNA expression profiles in pheochromocytoma and paraganglioma identifies genotype-specific markers and potentially regulated pathways.

de Cubas AA, Leandro-García LJ, Schiavi F, Mancikova V, Comino-Méndez I, Inglada-Pérez L, Perez-Martinez M, Ibarz N, Ximénez-Embún P, López-Jiménez E, Maliszewska A, Letón R, Gómez Graña A, Bernal C, Alvarez-Escolá C, Rodríguez-Antona C, Opocher G, Muñoz J, Megias D, Cascón A, Robledo M.

Endocr Relat Cancer. 2013 Jun 24;20(4):477-93. doi: 10.1530/ERC-12-0183. Print 2013 Aug.

PubMed [citation]

PMID:: 23660872

Details of each submission

From Ambry Genetics, SCV002751678.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.G93R variant (also known as c.277G>C), located in coding exon 1 of the VHL gene, results from a G to C substitution at nucleotide position 277. The glycine at codon 93 is replaced by arginine, an amino acid with dissimilar properties. This alteration, also designated as 490G>C in the literature, has been reported in multiple individuals having or suspected of having a diagnosis of VHL (Klein B et al. Hum. Genet. 2001 May;108:376-84; de Cubas AA et al. Endocr. Relat. Cancer. 2013 Aug;20:477-93; Bausch B et al. J Transl Med Epidemiol. 2014 2(1):1019.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: Sep 29, 2024

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