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NM_000551.4(VHL):c.554A>G (p.Tyr185Cys) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Sep 4, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000236099.9

Allele description [Variation Report for NM_000551.4(VHL):c.554A>G (p.Tyr185Cys)]

NM_000551.4(VHL):c.554A>G (p.Tyr185Cys)

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.554A>G (p.Tyr185Cys)
HGVS:
  • NC_000003.12:g.10149877A>G
  • NG_008212.3:g.13243A>G
  • NG_046756.1:g.7639A>G
  • NM_000551.4:c.554A>GMANE SELECT
  • NM_001354723.2:c.*108A>G
  • NM_198156.3:c.431A>G
  • NP_000542.1:p.Tyr185Cys
  • NP_000542.1:p.Tyr185Cys
  • NP_937799.1:p.Tyr144Cys
  • LRG_322t1:c.554A>G
  • LRG_322:g.13243A>G
  • LRG_322p1:p.Tyr185Cys
  • NC_000003.11:g.10191561A>G
  • NM_000551.3:c.554A>G
  • p.[Tyr185Cys]
Protein change:
Y144C
Links:
dbSNP: rs561874453
NCBI 1000 Genomes Browser:
rs561874453
Molecular consequence:
  • NM_001354723.2:c.*108A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000551.4:c.554A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.431A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000293700GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)		Uncertain significance
(Sep 4, 2024) 		germlineclinical testing

Citation Link,

SCV004221485Quest Diagnostics Nichols Institute San Juan Capistrano
criteria provided, single submitter

(Quest Diagnostics criteria)		Uncertain significance
(Aug 8, 2018) 		unknownclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular subtypes of clear cell renal cell carcinoma are associated with sunitinib response in the metastatic setting.

Beuselinck B, Job S, Becht E, Karadimou A, Verkarre V, Couchy G, Giraldo N, Rioux-Leclercq N, Molinié V, Sibony M, Elaidi R, Teghom C, Patard JJ, Méjean A, Fridman WH, Sautès-Fridman C, de Reyniès A, Oudard S, Zucman-Rossi J.

Clin Cancer Res. 2015 Mar 15;21(6):1329-39. doi: 10.1158/1078-0432.CCR-14-1128. Epub 2015 Jan 12.

PubMed [citation]
PMID:
25583177

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

Details of each submission

From GeneDx, SCV000293700.15

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with clear cell renal cell carcinoma (PMID: 25583177); This variant is associated with the following publications: (PMID: 26933808, 25583177)

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004221485.1

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

Description

The frequency of this variant in the general population, 0.000046 (6/129170 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with renal cell carcinoma (PMID: 25583177 (2015)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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

Last Updated: Oct 8, 2024