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NM_000551.4(VHL):c.427G>C (p.Asp143His) AND Von Hippel-Lindau syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 30, 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:
RCV003998849.2

Allele description [Variation Report for NM_000551.4(VHL):c.427G>C (p.Asp143His)]

NM_000551.4(VHL):c.427G>C (p.Asp143His)

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.427G>C (p.Asp143His)
HGVS:
  • NC_000003.12:g.10146600G>C
  • NG_008212.3:g.9966G>C
  • NG_046756.1:g.4362G>C
  • NM_000551.4:c.427G>CMANE SELECT
  • NM_001354723.2:c.*18-3187G>C
  • NM_198156.3:c.341-3187G>C
  • NP_000542.1:p.Asp143His
  • NP_000542.1:p.Asp143His
  • LRG_322t1:c.427G>C
  • LRG_322:g.9966G>C
  • LRG_322p1:p.Asp143His
  • NC_000003.11:g.10188284G>C
  • NM_000551.3:c.427G>C
Protein change:
D143H
Links:
dbSNP: rs372757722
NCBI 1000 Genomes Browser:
rs372757722
Molecular consequence:
  • NM_001354723.2:c.*18-3187G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_198156.3:c.341-3187G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000551.4:c.427G>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

Condition(s)

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004824838All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(May 30, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown3not providednot provided108544not providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004824838.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (1)

Description

This missense variant replaces aspartic acid with histidine at codon 143 of the VHL protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with VHL-related disorders in the literature. This variant has been identified in 1/251496 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided3not providednot providednot provided

Last Updated: Sep 29, 2024