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NM_000551.3(VHL):c.373C>T (p.His125Tyr)

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Interpretation:
Uncertain significance​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
4 (Most recent: Jul 4, 2021)
Last evaluated:
Jul 24, 2020
Accession:
VCV000411970.11
Variation ID:
411970
Description:
single nucleotide variant
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NM_000551.3(VHL):c.373C>T (p.His125Tyr)

Allele ID
393216
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p25.3
Genomic location
3: 10146546 (GRCh38) GRCh38 UCSC
3: 10188230 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000003.11:g.10188230C>T
NC_000003.12:g.10146546C>T
NG_008212.3:g.9912C>T
... more HGVS
Protein change
H125Y
Other names
-
Canonical SPDI
NC_000003.12:10146545:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Links
ClinGen: CA040676
dbSNP: rs375401722
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Jul 1, 2018 RCV000479517.4
Uncertain significance 1 criteria provided, single submitter Jul 24, 2020 RCV000462284.5
Uncertain significance 1 criteria provided, single submitter Aug 1, 2018 RCV000708764.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
VHL Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
551 1350
LOC107303340 - - - GRCh38 - 774

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Aug 01, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
GeneKor MSA
Accession: SCV000822211.1
Submitted: (Aug 08, 2018)
Evidence details
Uncertain significance
(Oct 23, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000565759.4
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted VHL c.373C>T at the cDNA level, p.His125Tyr (H125Y) at the protein level, and results in the change of a Histidine to … (more)
Uncertain significance
(Jul 24, 2020)
criteria provided, single submitter
Method: clinical testing
Von Hippel-Lindau syndrome
Erythrocytosis, familial, 2
Allele origin: germline
Invitae
Accession: SCV000553399.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces histidine with tyrosine at codon 125 of the VHL protein (p.His125Tyr). The histidine residue is weakly conserved and there is a … (more)
Uncertain significance
(Jul 01, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV000892671.8
Submitted: (Jul 04, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations. Tsaousis GN BMC cancer 2019 PMID: 31159747
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532

Text-mined citations for rs375401722...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 07, 2021