NM_000551.4(VHL):c.233A>G (p.Asn78Ser) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Feb 2, 2024
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:: RCV000254892.23

Allele description [Variation Report for NM_000551.4(VHL):c.233A>G (p.Asn78Ser)]

NM_000551.4(VHL):c.233A>G (p.Asn78Ser)

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.233A>G (p.Asn78Ser)

Other names:

NM_000551.4(VHL):c.233A>G

HGVS:

NC_000003.12:g.10142080A>G
NG_008212.3:g.5446A>G
NM_000551.4:c.233A>GMANE SELECT
NM_001354723.2:c.233A>G
NM_198156.3:c.233A>G
NP_000542.1:p.Asn78Ser
NP_000542.1:p.Asn78Ser
NP_001341652.1:p.Asn78Ser
NP_937799.1:p.Asn78Ser
LRG_322t1:c.233A>G
LRG_322:g.5446A>G
LRG_322p1:p.Asn78Ser
NC_000003.11:g.10183764A>G
NM_000551.3:c.233A>G
P40337:p.Asn78Ser
p.[Asn78Ser]

Protein change:

N78S

Links:

UniProtKB: P40337#VAR_005683; dbSNP: rs5030804

NCBI 1000 Genomes Browser:

rs5030804

Molecular consequence:

NM_000551.4:c.233A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354723.2:c.233A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.233A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Mus musculus ribonuclease, RNase A family 4 (Rnase4), transcript variant 2, mRNA
Mus musculus ribonuclease, RNase A family 4 (Rnase4), transcript variant 2, mRNA
gi|141802794|ref|NM_201239.2|

Nucleotide
UGDH [Pteropus giganteus]
UGDH [Pteropus giganteus]
Gene ID:120587987

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000111077	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (May 3, 2017)	germline	clinical testing	Citation Link,
SCV000322000	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Sep 13, 2022)	germline	clinical testing	Citation Link,
SCV000805330	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 6, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005198987	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 2, 2024)	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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	5	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 Eurofins Ntd Llc (ga), SCV000111077.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	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	germline	unknown	not provided	not provided	not provided		5	not provided	not provided	not provided

From GeneDx, SCV000322000.9

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

Description

Published functional studies demonstrate a damaging effect: an unstable protein resulting in up-regulation of HIF-2a and Glut-1, down-regulation of P27, and the disruption of pVHL and hVDU1 interactions in vitro (Li et al., 2002; Bangiyeva et al., 2009; Rechsteiner et al., 2011); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 446A>G; This variant is associated with the following publications: (PMID: 8730290, 16775032, 8707293, 19602254, 18836774, 23757202, 8634692, 7553625, 15300849, 17661816, 11409863, 12202531, 7591282, 10567493, 17024664, 14767899, 21362373, 9452106, 21454469, 11739384, 21715564, 10408776, 7728151, 25563310, 23842656, 27530247, 27439424, 26984080, 27527340, 12114495, 15109448, 30338240, 30787465, 8956040, 33720516, 18446368, 20233476, 28559085, 32742360)

#	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 PreventionGenetics, part of Exact Sciences, SCV000805330.1

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

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005198987.1

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

#	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

Last Updated: Oct 13, 2024

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