NM_000551.4(VHL):c.439A>G (p.Ile147Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 5, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000562695.7

Allele description [Variation Report for NM_000551.4(VHL):c.439A>G (p.Ile147Val)]

NM_000551.4(VHL):c.439A>G (p.Ile147Val)

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.439A>G (p.Ile147Val)

HGVS:

NC_000003.12:g.10146612A>G
NG_008212.3:g.9978A>G
NG_046756.1:g.4374A>G
NM_000551.4:c.439A>GMANE SELECT
NM_001354723.2:c.*18-3175A>G
NM_198156.3:c.341-3175A>G
NP_000542.1:p.Ile147Val
NP_000542.1:p.Ile147Val
LRG_322t1:c.439A>G
LRG_322:g.9978A>G
LRG_322p1:p.Ile147Val
NC_000003.11:g.10188296A>G
NM_000551.2:c.439A>G
NM_000551.3:c.439A>G

Protein change:

I147V

Links:

dbSNP: rs1057517560

NCBI 1000 Genomes Browser:

rs1057517560

Molecular consequence:

NM_001354723.2:c.*18-3175A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_198156.3:c.341-3175A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000551.4:c.439A>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
SCV000675798	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 5, 2023)	germline	clinical testing	Citation Link,
SCV002534174	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Aug 17, 2021)	germline	curation	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

SCV000675798

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 5, 2023)

germline

clinical testing

Citation Link,

SCV002534174

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Aug 17, 2021)

germline

curation

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, curation

Citations

PubMed

Bilateral renal tumors; conventional clear cell carcinoma and contralateral t(6;11)/t(X;17)-like tumor Histomorphologic, immunohistochemical, ultrastructural and molecular genetic studies including the report of a novel mutation in the VHL gene.

Petersson F, Michal M, Vaněček T, Hora M, Trivunic S, Halbhuber Z, Hes O.

Ann Diagn Pathol. 2011 Oct;15(5):362-9. doi: 10.1016/j.anndiagpath.2010.05.004. Epub 2010 Aug 14.

PubMed [citation]

PMID:: 20952280

Details of each submission

From Ambry Genetics, SCV000675798.6

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

Description

The p.I147V variant (also known as c.439A>G), located in coding exon 2 of the VHL gene, results from an A to G substitution at nucleotide position 439. The isoleucine at codon 147 is replaced by valine, an amino acid with highly similar properties. This variant has been previously reported in a 34-year-old woman with bilateral renal cancer (Petersson F et al. Ann Diagn Pathol. 2011 Oct;15(5):362-9). This amino acid position is 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

From Sema4, Sema4, SCV002534174.1

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

#	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: Jun 17, 2024

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