NM_000551.4(VHL):c.434A>G (p.Gln145Arg) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 12, 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:: RCV003020565.2

Allele description [Variation Report for NM_000551.4(VHL):c.434A>G (p.Gln145Arg)]

NM_000551.4(VHL):c.434A>G (p.Gln145Arg)

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.434A>G (p.Gln145Arg)

HGVS:

NC_000003.12:g.10146607A>G
NG_008212.3:g.9973A>G
NG_046756.1:g.4369A>G
NM_000551.4:c.434A>GMANE SELECT
NM_001354723.2:c.*18-3180A>G
NM_198156.3:c.341-3180A>G
NP_000542.1:p.Gln145Arg
NP_000542.1:p.Gln145Arg
LRG_322t1:c.434A>G
LRG_322:g.9973A>G
LRG_322p1:p.Gln145Arg
NC_000003.11:g.10188291A>G
NM_000551.3:c.434A>G
NR_176335.1:n.763A>G

Protein change:

Q145R

Molecular consequence:

NM_001354723.2:c.*18-3180A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_198156.3:c.341-3180A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000551.4:c.434A>G - missense variant - [Sequence Ontology: SO:0001583]

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

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003301407	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 12, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003301407

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 12, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, SCV003301407.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

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. 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) performed at Invitae indicates that this missense variant is expected to disrupt VHL protein function. ClinVar contains an entry for this variant (Variation ID: 2089752). This variant has not been reported in the literature in individuals affected with VHL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 145 of the VHL protein (p.Gln145Arg).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2024

ClinVar

Relating variation to medicine