NM_000551.4(VHL):c.548C>T (p.Ser183Leu) AND Chuvash polycythemia

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 29, 2022
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:: RCV001007624.9

Allele description [Variation Report for NM_000551.4(VHL):c.548C>T (p.Ser183Leu)]

NM_000551.4(VHL):c.548C>T (p.Ser183Leu)

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.548C>T (p.Ser183Leu)

HGVS:

NC_000003.12:g.10149871C>T
NG_008212.3:g.13237C>T
NG_046756.1:g.7633C>T
NM_000551.4:c.548C>TMANE SELECT
NM_001354723.2:c.*102C>T
NM_198156.3:c.425C>T
NP_000542.1:p.Ser183Leu
NP_000542.1:p.Ser183Leu
NP_937799.1:p.Ser142Leu
LRG_322t1:c.548C>T
LRG_322:g.13237C>T
LRG_322p1:p.Ser183Leu
NC_000003.11:g.10191555C>T
NM_000551.3:c.548C>T

Protein change:

S142L; SER183LEU

Links:

OMIM: 608537.0029; dbSNP: rs5030823

NCBI 1000 Genomes Browser:

rs5030823

Molecular consequence:

NM_001354723.2:c.*102C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000551.4:c.548C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.425C>T - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001167312	OMIM	no assertion criteria provided	Pathogenic (Mar 5, 2020)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004208793	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 29, 2022)	unknown	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

SCV001167312

OMIM

no assertion criteria provided

Pathogenic
(Mar 5, 2020)

germline

literature only

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

SCV004208793

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 29, 2022)

unknown

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Dysregulation of the HIF pathway due to VHL mutation causing severe erythrocytosis and pulmonary arterial hypertension.

Bond J, Gale DP, Connor T, Adams S, de Boer J, Gascoyne DM, Williams O, Maxwell PH, Ancliff PJ.

Blood. 2011 Mar 31;117(13):3699-701. doi: 10.1182/blood-2010-12-327569. No abstract available.

PubMed [citation]

PMID:: 21454469

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 OMIM, SCV001167312.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

For discussion of the c.548C-T transition in exon 3 of the VHL gene, resulting in a ser138-to-leu (S183L) substitution, that was found in compound heterozygous state in a patient with familial erythrocytosis-2 (ECYT2; 263400) by Bond et al. (2011), see 608537.0028.

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

From Baylor Genetics, SCV004208793.1

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

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

Last Updated: Oct 26, 2024

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