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NM_000551.4(VHL):c.235C>A (p.Arg79Ser) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 18, 2024
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:
RCV002829941.3

Allele description [Variation Report for NM_000551.4(VHL):c.235C>A (p.Arg79Ser)]

NM_000551.4(VHL):c.235C>A (p.Arg79Ser)

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.235C>A (p.Arg79Ser)
HGVS:
  • NC_000003.12:g.10142082C>A
  • NG_008212.3:g.5448C>A
  • NM_000551.4:c.235C>AMANE SELECT
  • NM_001354723.2:c.235C>A
  • NM_198156.3:c.235C>A
  • NP_000542.1:p.Arg79Ser
  • NP_000542.1:p.Arg79Ser
  • NP_001341652.1:p.Arg79Ser
  • NP_937799.1:p.Arg79Ser
  • LRG_322t1:c.235C>A
  • LRG_322:g.5448C>A
  • LRG_322p1:p.Arg79Ser
  • NC_000003.11:g.10183766C>A
  • NM_000551.3:c.235C>A
  • NR_176335.1:n.305C>A
Protein change:
R79S
Molecular consequence:
  • NM_000551.4:c.235C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354723.2:c.235C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.235C>A - 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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003212820Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jan 18, 2024) 		germlineclinical testing

PubMed (3)
[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

Congenital polycythemia with homozygous and heterozygous mutations of von Hippel-Lindau gene: five new Caucasian patients.

Bento MC, Chang KT, Guan Y, Liu E, Caldas G, Gatti RA, Prchal JT.

Haematologica. 2005 Jan;90(1):128-9.

PubMed [citation]
PMID:
15642680

Genotype-phenotype correlations, and retinal function and structure in von Hippel-Lindau disease.

Wittström E, Nordling M, Andréasson S.

Ophthalmic Genet. 2014 Jun;35(2):91-106. doi: 10.3109/13816810.2014.886265. Epub 2014 Feb 20.

PubMed [citation]
PMID:
24555745
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003212820.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 79 of the VHL protein (p.Arg79Ser). 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. ClinVar contains an entry for this variant (Variation ID: 2014245). 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 with a positive predictive value of 95%. This variant disrupts the p.Arg79 amino acid residue in VHL. Other variant(s) that disrupt this residue have been observed in individuals with VHL-related conditions (PMID: 15642680, 24555745), which suggests that this may be a clinically significant amino acid residue. 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.

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

Last Updated: Sep 29, 2024