NM_000551.4(VHL):c.538A>G (p.Ile180Val) AND Von Hippel-Lindau syndrome

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Aug 28, 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:: RCV000148921.9

Allele description [Variation Report for NM_000551.4(VHL):c.538A>G (p.Ile180Val)]

NM_000551.4(VHL):c.538A>G (p.Ile180Val)

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.538A>G (p.Ile180Val)

HGVS:

NC_000003.12:g.10149861A>G
NG_008212.3:g.13227A>G
NG_046756.1:g.7623A>G
NM_000551.4:c.538A>GMANE SELECT
NM_001354723.2:c.*92A>G
NM_198156.3:c.415A>G
NP_000542.1:p.Ile180Val
NP_000542.1:p.Ile180Val
NP_937799.1:p.Ile139Val
LRG_322t1:c.538A>G
LRG_322:g.13227A>G
LRG_322p1:p.Ile180Val
NC_000003.11:g.10191545A>G
NM_000551.3:c.538A>G
P40337:p.Ile180Val

Protein change:

I139V

Links:

UniProtKB: P40337#VAR_005770; dbSNP: rs377715747

NCBI 1000 Genomes Browser:

rs377715747

Molecular consequence:

NM_001354723.2:c.*92A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000551.4:c.538A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.415A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Von Hippel-Lindau syndrome (VHLS)
Synonyms:: VHL syndrome; Von Hippel-Lindau
Identifiers:: MONDO: MONDO:0008667; MedGen: C0019562; Orphanet: 892; OMIM: 193300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001136313	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Uncertain significance (Apr 11, 2023)	unknown	clinical testing	Citation Link,
SCV005382208	Institute of Immunology and Genetics Kaiserslautern	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 28, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001136313

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Uncertain significance
(Apr 11, 2023)

unknown

clinical testing

Citation Link,

SCV005382208

Institute of Immunology and Genetics Kaiserslautern

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 28, 2023)

germline

clinical testing

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

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	research
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From CSER _CC_NCGL, University of Washington - ESP 6500 variant annotation, SCV000190678.1

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

#	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 Mendelics, SCV001136313.2

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

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

From Institute of Immunology and Genetics Kaiserslautern, SCV005382208.1

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

Description

ACMG Criteria: PM1, PM2, PP3; Variant was found in a heterozygous state

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

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000190678	CSER _CC_NCGL, University of Washington - ESP 6500 variant annotation	flagged submission Reason: Outlier claim with insufficient supporting evidence Notes: None	Likely benign (Jun 1, 2014)	germline	research

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000190678

CSER _CC_NCGL, University of Washington - ESP 6500 variant annotation

flagged submission

Reason: Outlier claim with insufficient supporting evidence

Notes: None

Likely benign
(Jun 1, 2014)

germline

research

Last Updated: Nov 3, 2024

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