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NM_000551.4(VHL):c.224TCT[1] (p.Phe76del) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 28, 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:
RCV002444839.2

Allele description [Variation Report for NM_000551.4(VHL):c.224TCT[1] (p.Phe76del)]

NM_000551.4(VHL):c.224TCT[1] (p.Phe76del)

Gene:
VHL:von Hippel-Lindau tumor suppressor [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
3p25.3
Genomic location:
Preferred name:
NM_000551.4(VHL):c.224TCT[1] (p.Phe76del)
HGVS:
  • NC_000003.11:g.10183755_10183757del
  • NC_000003.12:g.10142071TCT[1]
  • NG_008212.3:g.5437TCT[1]
  • NM_000551.4:c.224TCT[1]MANE SELECT
  • NM_000551.4:c.227_229delTCT
  • NM_001354723.2:c.224TCT[1]
  • NM_198156.3:c.224TCT[1]
  • NP_000542.1:p.Phe76del
  • NP_001341652.1:p.Phe76del
  • NP_937799.1:p.Phe76del
  • LRG_322t1:c.227_229del
  • LRG_322:g.5437TCT[1]
  • NC_000003.11:g.10183755TCT[1]
  • NC_000003.11:g.10183755_10183757del
  • NC_000003.11:g.10183758_10183760delTCT
  • NM_000551.3:c.227_229del
  • NM_000551.3:c.227_229delTCT
  • NM_000551.4:c.227_229delMANE SELECT
  • NM_000551.4:c.227_229delTCTMANE SELECT
  • c.583C>T
  • p.[Phe76del]
Protein change:
F76del; GLN195TER
Links:
dbSNP: rs5030648
NCBI 1000 Genomes Browser:
rs5030648
Molecular consequence:
  • NM_000551.4:c.224TCT[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001354723.2:c.224TCT[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_198156.3:c.224TCT[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002734017Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Sep 28, 2019) 		germlineclinical testing

PubMed (15)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mosaicism in von Hippel-Lindau disease: lessons from kindreds with germline mutations identified in offspring with mosaic parents.

Sgambati MT, Stolle C, Choyke PL, Walther MM, Zbar B, Linehan WM, Glenn GM.

Am J Hum Genet. 2000 Jan;66(1):84-91.

PubMed [citation]
PMID:
10631138
PMCID:
PMC1288351

Germline mutations in the von Hippel-Lindau (VHL) gene in patients from Poland: disease presentation in patients with deletions of the entire VHL gene.

Cybulski C, Krzystolik K, Murgia A, Górski B, Debniak T, Jakubowska A, Martella M, Kurzawski G, Prost M, Kojder I, Limon J, Nowacki P, Sagan L, Białas B, Kałuza J, Zdunek M, Omulecka A, Jaskólski D, Kostyk E, Koraszewska-Matuszewska B, Haus O, Janiszewska H, et al.

J Med Genet. 2002 Jul;39(7):E38. No abstract available.

PubMed [citation]
PMID:
12114495
PMCID:
PMC1735187
See all PubMed Citations (15)

Details of each submission

From Ambry Genetics, SCV002734017.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (15)

Description

The c.227_229delTCT pathogenic mutation (also known as c.226_228del TTC or p.F76del) is located in coding exon 1 of the VHL gene. This pathogenic mutation results from an in-frame TCT deletion at nucleotide positions 227 to 229. This results in the in-frame deletion of a phenylalanine at codon 76. This pathogenic variant has been identified in numerous individuals and families diagnosed with VHL (Rocha J et al. J. Med. Genet. 2003 Mar; 40(3):e31; Sgambati M et al. Am. J. Hum. Genet. 2000 Jan; 66(1):84-91; Gomy I et al. Fam. Cancer. 2010 Dec; 9(4):635-42; Hes F et al. Clin. Genet. 2007 Aug; 72(2):122-9; Rasmussen A et al. BMC Med. Genet. 2010 Jan 12;11:4; Pandit R et al. Eur. J. Endocrinol. 2016 Oct;175:311-23; Wong M et al. Chin J Cancer. 2016 Aug;35:79; Wang Y et al. Oncol Lett. 2018 Apr;15:4882-4890). Molecular dynamics studies indicate that the phenyalanine at amino acid position 76, which is deleted by this alteration, plays a key role in the structural integrity of the beta-domain of the VHL protein (Limaverde-Sousa G et al. Proteins. 2013 Feb; 81(2):349-63). Of note, this pathogenic variant may be referred to as c.224_226delTCT in some literature. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 26, 2024