NM_000551.4(VHL):c.278_279delinsTT (p.Gly93Val) AND Hereditary cancer-predisposing syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 18, 2020
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:: RCV001016587.3

Allele description

NM_000551.4(VHL):c.278_279delinsTT (p.Gly93Val)

Gene:

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

Variant type:

Indel

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_000551.4(VHL):c.278_279delinsTT (p.Gly93Val)

HGVS:

NC_000003.12:g.10142125_10142126delinsTT
NG_008212.3:g.5491_5492delinsTT
NM_000551.4:c.278_279delinsTTMANE SELECT
NM_001354723.2:c.278_279delinsTT
NM_198156.3:c.278_279delinsTT
NP_000542.1:p.Gly93Val
NP_001341652.1:p.Gly93Val
NP_937799.1:p.Gly93Val
LRG_322:g.5491_5492delinsTT
NC_000003.11:g.10183809_10183810delinsTT
NM_000551.3:c.278_279delGCinsTT

Protein change:

G93V

Links:

dbSNP: rs1559426072

NCBI 1000 Genomes Browser:

rs1559426072

Molecular consequence:

NM_000551.4:c.278_279delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001354723.2:c.278_279delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.278_279delinsTT - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

Recent activity

Clear Turn Off Turn On

txid1423[orgn] AND "strain 3026O2"[All Fields] (1)
PopSet
Bacteria 16S ribosomal RNA gene, partial sequence.
Bacteria 16S ribosomal RNA gene, partial sequence.
PopSet: 585283029

PopSet
Nucleotide Links for OMIM (Select 203780) (34)
Nucleotide
CREB3 regulatory factor isoform X1 [Mus musculus]
CREB3 regulatory factor isoform X1 [Mus musculus]
gi|1039754778|ref|XP_017173212.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001177553	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Likely pathogenic (Jun 18, 2020)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 10095351, 11409863, 12000816, 17922902, 20151405, 22136840, 7728151, 8707293, 8956040 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001177553

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Likely pathogenic
(Jun 18, 2020)

germline

clinical testing

PubMed (9)
[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	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

[Retinal capillary angioma. Clinical and molecular genetic studies].

Kreusel KM, Bornfeld N, Bender BU, Neumann L, Foerster MH, Neumann HP.

Ophthalmologe. 1999 Feb;96(2):71-6. German.

PubMed [citation]

PMID:: 10095351

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

See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV001177553.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (9)

Description

The c.278_279delGCinsTT variant (also known as p.G93V), located in coding exon 1 of the VHL gene, results from an in-frame deletion of GC and insertion of TT at nucleotide positions 278 to 279. This results in the substitution of the glycine residue for a valine residue at codon 93, an amino acid with dissimilar properties. An variant resulting in the same amino acid substitution, p.G93V (c.278G>T), has been reported in a cohort of patients with non-syndromic pheochromocytoma (Neumann HP et al. N. Engl. J. Med., 2002 May;346:1459-66). Further, other missense variants at this codon (p.G93D, p.G93S, p.G93R, p.G93C) have been reported in numerous individuals with personal and/or family history consistent with Von Hippel-Lindau syndrome (VHL) (Chen F et al. Hum. Mutat., 1995;5:66-75; Zbar B et al. Hum. Mutat., 1996;8:348-57; Glavac D et al. Hum. Genet., 1996 Sep;98:271-80; Neumann HP et al. N. Engl. J. Med., 2002 May;346:1459-66; Klein B et al. Hum. Genet., 2001 May;108:376-84; Schreinemakers JM et al. World J Surg Oncol, 2007 Oct;5:112; Iacobone M et al. Surgery, 2011 Dec;150:1194-201). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). 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	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Mar 5, 2024

ClinVar

Relating variation to medicine