NM_000551.4(VHL):c.488T>G (p.Leu163Arg) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Oct 25, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000474133.1

Allele description [Variation Report for NM_000551.4(VHL):c.488T>G (p.Leu163Arg)]

NM_000551.4(VHL):c.488T>G (p.Leu163Arg)

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.488T>G (p.Leu163Arg)
HGVS:
  • NC_000003.12:g.10149811T>G
  • NG_008212.3:g.13177T>G
  • NG_046756.1:g.7573T>G
  • NM_000551.3:c.488T>G
  • NM_000551.4:c.488T>GMANE SELECT
  • NM_001354723.2:c.*42T>G
  • NM_198156.3:c.365T>G
  • NP_000542.1:p.Leu163Arg
  • NP_000542.1:p.Leu163Arg
  • NP_937799.1:p.Leu122Arg
  • LRG_322t1:c.488T>G
  • LRG_322:g.13177T>G
  • LRG_322p1:p.Leu163Arg
  • NC_000003.11:g.10191495T>G
Protein change:
L122R
Links:
dbSNP: rs28940297
NCBI 1000 Genomes Browser:
rs28940297
Molecular consequence:
  • NM_001354723.2:c.*42T>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000551.3:c.488T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000551.4:c.488T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.365T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Erythrocytosis, familial, 2 (ECYT2)
Synonyms:
POLYCYTHEMIA, CHUVASH TYPE; POLYCYTHEMIA, VHL-DEPENDENT
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

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000553373Invitaecriteria provided, single submitter
Uncertain significance
(Oct 25, 2016)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000553373.2

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

Description

This sequence change replaces leucine with arginine at codon 163 of the VHL protein (p.Leu163Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in two individuals affected with pheochromocytoma from a single family (PMID: 156007616). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 25, 2021

Support Center