NM_001354723.2(VHL):c.*171_*172delinsAG AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Aug 2, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000461877.1

Allele description [Variation Report for NM_001354723.2(VHL):c.*171_*172delinsAG]

NM_001354723.2(VHL):c.*171_*172delinsAG

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:
Indel
Cytogenetic location:
3p25.3
Genomic location:
Preferred name:
NM_001354723.2(VHL):c.*171_*172delinsAG
HGVS:
  • NC_000003.12:g.10149940_10149941delinsAG
  • NG_008212.3:g.13306_13307delinsAG
  • NG_046756.1:g.7702_7703delinsAG
  • NM_001354723.2:c.*171_*172delinsAG
  • NM_198156.3:c.494_495delinsAG
  • NP_937799.1:p.Ile165Lys
  • LRG_322t1:c.617_618delinsAG
  • LRG_322:g.13306_13307delinsAG
  • LRG_322p1:p.Ile206Lys
  • NC_000003.11:g.10191624_10191625delinsAG
Protein change:
I165K
Links:
dbSNP: rs1060503567
NCBI 1000 Genomes Browser:
rs1060503567
Molecular consequence:
  • NM_001354723.2:c.*171_*172delinsAG - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_198156.3:c.494_495delinsAG - 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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000553418Invitaecriteria provided, single submitter
Uncertain significance
(Aug 2, 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, SCV000553418.2

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

Description

This sequence change replaces isoleucine with lysine at codon 206 of the VHL protein (p.Ile206Lys). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and lysine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a VHL-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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: May 10, 2021

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