NM_000551.4(VHL):c.203C>T (p.Ser68Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 13, 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:: RCV002422648.3

Allele description [Variation Report for NM_000551.4(VHL):c.203C>T (p.Ser68Leu)]

NM_000551.4(VHL):c.203C>T (p.Ser68Leu)

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.203C>T (p.Ser68Leu)

HGVS:

NC_000003.12:g.10142050C>T
NG_008212.3:g.5416C>T
NM_000551.4:c.203C>TMANE SELECT
NM_001354723.2:c.203C>T
NM_198156.3:c.203C>T
NP_000542.1:p.Ser68Leu
NP_000542.1:p.Ser68Leu
NP_001341652.1:p.Ser68Leu
NP_937799.1:p.Ser68Leu
LRG_322t1:c.203C>T
LRG_322:g.5416C>T
LRG_322p1:p.Ser68Leu
NC_000003.11:g.10183734C>T
NM_000551.3:c.203C>T

Protein change:

S68L

Links:

dbSNP: rs869025617

NCBI 1000 Genomes Browser:

rs869025617

Molecular consequence:

NM_000551.4:c.203C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354723.2:c.203C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.203C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002720273	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17661816, 27785399 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002720273

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 13, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Frequency of Von Hippel-Lindau germline mutations in classic and non-classic Von Hippel-Lindau disease identified by DNA sequencing, Southern blot analysis and multiplex ligation-dependent probe amplification.

Hes FJ, van der Luijt RB, Janssen AL, Zewald RA, de Jong GJ, Lenders JW, Links TP, Luyten GP, Sijmons RH, Eussen HJ, Halley DJ, Lips CJ, Pearson PL, van den Ouweland AM, Majoor-Krakauer DF.

Clin Genet. 2007 Aug;72(2):122-9. Erratum in: Clin Genet. 2008 Apr;73(4):399.

PubMed [citation]

PMID:: 17661816

Von Hippel-Lindau disease: the clinical manifestations and genetic analysis results of two cases from a single family.

Kinyas S, Ozal SA, Guclu H, Gurlu V, Esgin H, Gurkan H.

Balkan J Med Genet. 2015 Dec 1;18(2):65-70.

PubMed [citation]

PMID:: 27785399
PMCID:: PMC5026270

Details of each submission

From Ambry Genetics, SCV002720273.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.S68L variant (also known as c.203C>T), located in coding exon 1 of the VHL gene, results from a C to T substitution at nucleotide position 203. The serine at codon 68 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been detected in an individual with a personal history of pheochromocytoma and paraganglioma (Ambry internal data). Another alteration at this same codon, p.S68P, has been reported in patients with VHL-associated features (Hes FJ et al. Clin Genet, 2007 Aug;72:122-9; Kinyas S et al. Balkan J Med Genet, 2015 Dec;18:65-70). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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