NM_000551.4(VHL):c.393C>A (p.Asn131Lys) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Oct 26, 2020
Review status:: criteria provided, conflicting classifications

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:: RCV000482784.5

Allele description [Variation Report for NM_000551.4(VHL):c.393C>A (p.Asn131Lys)]

NM_000551.4(VHL):c.393C>A (p.Asn131Lys)

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.393C>A (p.Asn131Lys)

HGVS:

NC_000003.12:g.10146566C>A
NG_008212.3:g.9932C>A
NG_046756.1:g.4328C>A
NM_000551.4:c.393C>AMANE SELECT
NM_001354723.2:c.*18-3221C>A
NM_198156.3:c.341-3221C>A
NP_000542.1:p.Asn131Lys
NP_000542.1:p.Asn131Lys
LRG_322t1:c.393C>A
LRG_322:g.9932C>A
LRG_322p1:p.Asn131Lys
NC_000003.11:g.10188250C>A
NM_000551.3:c.393C>A

Protein change:

N131K

Links:

dbSNP: rs1064794272

NCBI 1000 Genomes Browser:

rs1064794272

Molecular consequence:

NM_001354723.2:c.*18-3221C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_198156.3:c.341-3221C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000551.4:c.393C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000568591	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Oct 26, 2020)	germline	clinical testing	Citation Link,
SCV000697510	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Feb 9, 2016)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22105611, 15300849, 9829912, 21384277 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000568591

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Oct 26, 2020)

germline

clinical testing

Citation Link,

SCV000697510

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Feb 9, 2016)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Pilot trial of sunitinib therapy in patients with von Hippel-Lindau disease.

Jonasch E, McCutcheon IE, Waguespack SG, Wen S, Davis DW, Smith LA, Tannir NM, Gombos DS, Fuller GN, Matin SF.

Ann Oncol. 2011 Dec;22(12):2661-2666. doi: 10.1093/annonc/mdr011.

PubMed [citation]

PMID:: 22105611
PMCID:: PMC4542805

Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions.

Gallou C, Chauveau D, Richard S, Joly D, Giraud S, Olschwang S, Martin N, Saquet C, Chrétien Y, Méjean A, Correas JM, Benoît G, Colombeau P, Grünfeld JP, Junien C, Béroud C.

Hum Mutat. 2004 Sep;24(3):215-24. Erratum in: Hum Mutat. 2004 Nov;24(5):435-6.

PubMed [citation]

PMID:: 15300849

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000568591.5

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

Description

Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22105611, 15300849, 18836774, 9829912, 17661816, 24166983, 20660572, 17696210, 20151405, 19238077, 21384277, 29748190)

#	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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697510.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

#	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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