U.S. flag

An official website of the United States government

NM_000551.4(VHL):c.292T>A (p.Tyr98Asn) AND Von Hippel-Lindau syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 21, 2023
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:
RCV003388486.1

Allele description [Variation Report for NM_000551.4(VHL):c.292T>A (p.Tyr98Asn)]

NM_000551.4(VHL):c.292T>A (p.Tyr98Asn)

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.292T>A (p.Tyr98Asn)
HGVS:
  • NC_000003.12:g.10142139T>A
  • NG_008212.3:g.5505T>A
  • NM_000551.4:c.292T>AMANE SELECT
  • NM_001354723.2:c.292T>A
  • NM_198156.3:c.292T>A
  • NP_000542.1:p.Tyr98Asn
  • NP_000542.1:p.Tyr98Asn
  • NP_001341652.1:p.Tyr98Asn
  • NP_937799.1:p.Tyr98Asn
  • LRG_322t1:c.292T>A
  • LRG_322:g.5505T>A
  • LRG_322p1:p.Tyr98Asn
  • NC_000003.11:g.10183823T>A
  • NM_000551.3:c.292T>A
  • NR_176335.1:n.362T>A
Protein change:
Y98N
Molecular consequence:
  • NM_000551.4:c.292T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354723.2:c.292T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.292T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_176335.1:n.362T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Von Hippel-Lindau syndrome (VHLS)
Synonyms:
VHL syndrome; Von Hippel-Lindau
Identifiers:
MONDO: MONDO:0008667; MedGen: C0019562; Orphanet: 892; OMIM: 193300

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004100048Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Sep 21, 2023) 		germlineclinical testing

PubMed (2)
[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

Genotype and phenotype correlation in von Hippel-Lindau disease based on alteration of the HIF-α binding site in VHL protein.

Liu SJ, Wang JY, Peng SH, Li T, Ning XH, Hong BA, Liu JY, Wu PJ, Zhou BW, Zhou JC, Qi NN, Peng X, Zhang JF, Ma KF, Cai L, Gong K.

Genet Med. 2018 Oct;20(10):1266-1273. doi: 10.1038/gim.2017.261. Epub 2018 Mar 29.

PubMed [citation]
PMID:
29595810

PARS PLANA VITRECTOMY IN ADVANCED CASES OF VON HIPPEL-LINDAU EYE DISEASE.

Krzystolik K, Stopa M, Kuprjanowicz L, Drobek-Slowik M, Cybulski C, Jakubowska A, Gronwald J, Lubiński J, Lubiński W.

Retina. 2016 Feb;36(2):325-34. doi: 10.1097/IAE.0000000000000707.

PubMed [citation]
PMID:
26308528

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004100048.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: VHL c.292T>A (p.Tyr98Asn) results in a non-conservative amino acid change located in the von Hippel-Lindau disease tumour suppressor, beta/alpha domain (IPR022772) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 223372 control chromosomes (gnomAD). c.292T>A has been reported in the literature in multiple individuals affected with Von Hippel-Lindau Syndrome (examples: Liu_2018, Krzystolik_2016). Other variants affecting the same residue (p.Tyr98His, p.Tyr98Cys) have been classifed pathogenic internally and in ClinVar (CV IDs: 2223, 223176). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 29595810, 26308528). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Nov 4, 2023