NM_000551.4(VHL):c.347T>G (p.Leu116Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 11, 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:: RCV002450737.3

Allele description [Variation Report for NM_000551.4(VHL):c.347T>G (p.Leu116Arg)]

NM_000551.4(VHL):c.347T>G (p.Leu116Arg)

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.347T>G (p.Leu116Arg)

HGVS:

NC_000003.12:g.10146520T>G
NG_008212.3:g.9886T>G
NG_046756.1:g.4282T>G
NM_000551.4:c.347T>GMANE SELECT
NM_001354723.2:c.*18-3267T>G
NM_198156.3:c.341-3267T>G
NP_000542.1:p.Leu116Arg
NP_000542.1:p.Leu116Arg
LRG_322t1:c.347T>G
LRG_322:g.9886T>G
LRG_322p1:p.Leu116Arg
NC_000003.11:g.10188204T>G
NM_000551.3:c.347T>G

Protein change:

L116R

Links:

dbSNP: rs879254230

NCBI 1000 Genomes Browser:

rs879254230

Molecular consequence:

NM_001354723.2:c.*18-3267T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_198156.3:c.341-3267T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000551.4:c.347T>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
SCV002617595	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 11, 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

SCV002617595

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 11, 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

Structural basis of PROTAC cooperative recognition for selective protein degradation.

Gadd MS, Testa A, Lucas X, Chan KH, Chen W, Lamont DJ, Zengerle M, Ciulli A.

Nat Chem Biol. 2017 May;13(5):514-521. doi: 10.1038/nchembio.2329. Epub 2017 Mar 13.

PubMed [citation]

PMID:: 28288108
PMCID:: PMC5392356

Details of each submission

From Ambry Genetics, SCV002617595.3

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

Description

The p.L116R variant (also known as c.347T>G), located in coding exon 2 of the VHL gene, results from a T to G substitution at nucleotide position 347. The leucine at codon 116 is replaced by arginine, an amino acid with dissimilar properties. Based on internal structural analysis, this variant is anticipated to result in a significant decrease in structural stability (Ambry internal data; Gadd MS et al. Nat Chem Biol, 2017 05;13:514-521). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant 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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