NM_000551.4(VHL):c.415T>C (p.Ser139Pro) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 15, 2020
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:: RCV001318529.7

Allele description [Variation Report for NM_000551.4(VHL):c.415T>C (p.Ser139Pro)]

NM_000551.4(VHL):c.415T>C (p.Ser139Pro)

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.415T>C (p.Ser139Pro)

HGVS:

NC_000003.12:g.10146588T>C
NG_008212.3:g.9954T>C
NG_046756.1:g.4350T>C
NM_000551.4:c.415T>CMANE SELECT
NM_001354723.2:c.*18-3199T>C
NM_198156.3:c.341-3199T>C
NP_000542.1:p.Ser139Pro
LRG_322:g.9954T>C
NC_000003.11:g.10188272T>C

Protein change:

S139P

Links:

dbSNP: rs1696264596

NCBI 1000 Genomes Browser:

rs1696264596

Molecular consequence:

NM_001354723.2:c.*18-3199T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_198156.3:c.341-3199T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000551.4:c.415T>C - 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

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Homo sapiens POLR2F full length open reading frame (ORF) cDNA clone (cDNA clone ...
Homo sapiens POLR2F full length open reading frame (ORF) cDNA clone (cDNA clone C22ORF:pGEM.POLR2F)
gi|47678622|emb|CR456546.1|

Nucleotide
GJA5 gap junction protein alpha 5 [Homo sapiens]
GJA5 gap junction protein alpha 5 [Homo sapiens]
Gene ID:2702

Gene
Gene Links for GEO Profiles (Select 73648007) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001509235	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 15, 2020)	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

SCV001509235

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 15, 2020)

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001509235.4

#	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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with VHL-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with proline at codon 139 of the VHL protein (p.Ser139Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline.

#	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: Sep 29, 2024

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