U.S. flag

An official website of the United States government

NM_000551.4(VHL):c.571C>T (p.His191Tyr) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 14, 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:
RCV003794414.2

Allele description [Variation Report for NM_000551.4(VHL):c.571C>T (p.His191Tyr)]

NM_000551.4(VHL):c.571C>T (p.His191Tyr)

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.571C>T (p.His191Tyr)
HGVS:
  • NC_000003.12:g.10149894C>T
  • NG_008212.3:g.13260C>T
  • NG_046756.1:g.7656C>T
  • NM_000551.4:c.571C>TMANE SELECT
  • NM_001354723.2:c.*125C>T
  • NM_198156.3:c.448C>T
  • NP_000542.1:p.His191Tyr
  • NP_000542.1:p.His191Tyr
  • NP_937799.1:p.His150Tyr
  • LRG_322t1:c.571C>T
  • LRG_322:g.13260C>T
  • LRG_322p1:p.His191Tyr
  • NC_000003.11:g.10191578C>T
  • NM_000551.3:c.571C>T
  • NR_176335.1:n.900C>T
Protein change:
H150Y
Molecular consequence:
  • NM_001354723.2:c.*125C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000551.4:c.571C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.448C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_176335.1:n.900C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Chuvash polycythemia
Synonyms:
POLYCYTHEMIA, VHL-DEPENDENT; Erythrocytosis, familial, 2
Identifiers:
MONDO: MONDO:0009892; MedGen: C1837915; Orphanet: 238557; OMIM: 263400
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
SCV004585286Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 14, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

The myosin-bound form of protein phosphatase 1 (PP-1M) is the enzyme that dephosphorylates native myosin in skeletal and cardiac muscles.

Chisholm AA, Cohen P.

Biochim Biophys Acta. 1988 Sep 16;971(2):163-9.

PubMed [citation]
PMID:
2844285

Loss of JAK2 regulation via a heterodimeric VHL-SOCS1 E3 ubiquitin ligase underlies Chuvash polycythemia.

Russell RC, Sufan RI, Zhou B, Heir P, Bunda S, Sybingco SS, Greer SN, Roche O, Heathcote SA, Chow VW, Boba LM, Richmond TD, Hickey MM, Barber DL, Cheresh DA, Simon MC, Irwin MS, Kim WY, Ohh M.

Nat Med. 2011 Jun 19;17(7):845-53. doi: 10.1038/nm.2370.

PubMed [citation]
PMID:
21685897
PMCID:
PMC3221316
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004585286.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with VHL-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on VHL protein function. This variant disrupts the p.His191 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 2844285, 21685897, 23403324, 27651169). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 191 of the VHL protein (p.His191Tyr).

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

Last Updated: Sep 29, 2024