NM_000551.4(VHL):c.175C>T (p.Pro59Ser) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 2, 2015
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:: RCV000213269.1

Allele description [Variation Report for NM_000551.4(VHL):c.175C>T (p.Pro59Ser)]

NM_000551.4(VHL):c.175C>T (p.Pro59Ser)

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.175C>T (p.Pro59Ser)

HGVS:

NC_000003.12:g.10142022C>T
NG_008212.3:g.5388C>T
NM_000551.4:c.175C>TMANE SELECT
NM_001354723.2:c.175C>T
NM_198156.3:c.175C>T
NP_000542.1:p.Pro59Ser
NP_000542.1:p.Pro59Ser
NP_001341652.1:p.Pro59Ser
NP_937799.1:p.Pro59Ser
LRG_322t1:c.175C>T
LRG_322:g.5388C>T
LRG_322p1:p.Pro59Ser
NC_000003.11:g.10183706C>T
NM_000551.3:c.175C>T

Protein change:

P59S

Links:

dbSNP: rs876659041

NCBI 1000 Genomes Browser:

rs876659041

Molecular consequence:

NM_000551.4:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354723.2:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.175C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000275012	Ambry Genetics	criteria provided, single submitter (Ambry Autosomal Dominant and X-Linked criteria (10/2015))	Uncertain significance (Apr 2, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000275012

Ambry Genetics

criteria provided, single submitter

(Ambry Autosomal Dominant and X-Linked criteria (10/2015))

Uncertain significance
(Apr 2, 2015)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Identification and in silico analysis of novel von Hippel-Lindau (VHL) gene variants from a large population.

Leonardi E, Martella M, Tosatto SC, Murgia A.

Ann Hum Genet. 2011 Jul;75(4):483-96. doi: 10.1111/j.1469-1809.2011.00647.x. Epub 2011 Apr 4.

PubMed [citation]

PMID:: 21463266

Details of each submission

From Ambry Genetics, SCV000275012.5

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

Description

The p.P59S variant (also known as c.175C>T), located in coding exon 1 of the VHL gene, results from a C to T substitution at nucleotide position 175. The proline at codon 59 is replaced by serine, an amino acid with similar properties. This alteration has been reported in an individual with an isolated pheochromocytoma(Leonardi E et al. Ann Hum Genet. 2011 Jul;75(4):483-96).This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6283 samples (12566 alleles) with coverage at this position.To date, this alteration has been detected with an allele frequency of approximately 0.02% (greater than 4300alleles tested) in our clinical cohort. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis.Since supporting evidence is limited at this time, the clinical significance of p.P59Sremains unclear.<br />

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

Last Updated: Mar 5, 2024

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