NM_000551.4(VHL):c.406T>G (p.Phe136Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 26, 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:: RCV002321463.3

Allele description [Variation Report for NM_000551.4(VHL):c.406T>G (p.Phe136Val)]

NM_000551.4(VHL):c.406T>G (p.Phe136Val)

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.406T>G (p.Phe136Val)

HGVS:

NC_000003.12:g.10146579T>G
NG_008212.3:g.9945T>G
NG_046756.1:g.4341T>G
NM_000551.4:c.406T>GMANE SELECT
NM_001354723.2:c.*18-3208T>G
NM_198156.3:c.341-3208T>G
NP_000542.1:p.Phe136Val
NP_000542.1:p.Phe136Val
LRG_322t1:c.406T>G
LRG_322:g.9945T>G
LRG_322p1:p.Phe136Val
NC_000003.11:g.10188263T>G
NM_000551.3:c.406T>G
NR_176335.1:n.735T>G

Protein change:

F136V

Molecular consequence:

NM_001354723.2:c.*18-3208T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_198156.3:c.341-3208T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000551.4:c.406T>G - 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
SCV002628182	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Mar 26, 2024)	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

SCV002628182

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Mar 26, 2024)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Pheochromocytoma and multifocal functioning paraganglioma in a 9-year-old boy with von Hippel-Lindau disease.

Tröbs RB, Reichardt P, Friedrich T, Klöppel R, Bennek J.

Urol Int. 2002;68(4):299-301.

PubMed [citation]

PMID:: 12053037

Details of each submission

From Ambry Genetics, SCV002628182.3

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

Description

The p.F136V variant (also known as c.406T>G), located in coding exon 2 of the VHL gene, results from a T to G substitution at nucleotide position 406. The phenylalanine at codon 136 is replaced by valine, an amino acid with highly similar properties. This variant has been observed in multiple individuals with a personal history that is consistent with von Hippel-Lindau syndrome (VHL) (Tröbs RB et al. Urol Int, 2002;68:299-301; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	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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