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NM_000551.4(VHL):c.501_502insTTGTCCGT (p.Ser168fs) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 20, 2023
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:
RCV000818637.9

Allele description [Variation Report for NM_000551.4(VHL):c.501_502insTTGTCCGT (p.Ser168fs)]

NM_000551.4(VHL):c.501_502insTTGTCCGT (p.Ser168fs)

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:
Insertion
Cytogenetic location:
3p25.3
Genomic location:
Preferred name:
NM_000551.4(VHL):c.501_502insTTGTCCGT (p.Ser168fs)
HGVS:
  • NC_000003.12:g.10149824_10149825insTTGTCCGT
  • NG_008212.3:g.13190_13191insTTGTCCGT
  • NG_046756.1:g.7586_7587insTTGTCCGT
  • NM_000551.4:c.501_502insTTGTCCGTMANE SELECT
  • NM_001354723.2:c.*55_*56insTTGTCCGT
  • NM_198156.3:c.378_379insTTGTCCGT
  • NP_000542.1:p.Ser168fs
  • NP_000542.1:p.Ser168fs
  • NP_937799.1:p.Ser127fs
  • LRG_322t1:c.501_502insTTGTCCGT
  • LRG_322:g.13190_13191insTTGTCCGT
  • LRG_322p1:p.Ser168fs
  • NC_000003.11:g.10191508_10191509insTTGTCCGT
  • NM_000551.3:c.501_502insTTGTCCGT
  • p.[Ser168Leufs*5]
Protein change:
S127fs
Links:
dbSNP: rs398123483
NCBI 1000 Genomes Browser:
rs398123483
Molecular consequence:
  • NM_001354723.2:c.*55_*56insTTGTCCGT - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000551.4:c.501_502insTTGTCCGT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_198156.3:c.378_379insTTGTCCGT - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Chuvash polycythemia
Synonyms:
POLYCYTHEMIA, VHL-DEPENDENT; Erythrocytosis, familial, 2
Identifiers:
MONDO: MONDO:0009892; MedGen: C1837915; Orphanet: 238557; OMIM: 263400
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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000959261Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 20, 2023) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations in the VHL tumor suppressor gene and associated lesions in families with von Hippel-Lindau disease from central Europe.

Glavac D, Neumann HP, Wittke C, Jaenig H, Masek O, Streicher T, Pausch F, Engelhardt D, Plate KH, Höfler H, Chen F, Zbar B, Brauch H.

Hum Genet. 1996 Sep;98(3):271-80.

PubMed [citation]
PMID:
8707293

The impact of molecular genetic analysis of the VHL gene in patients with haemangioblastomas of the central nervous system.

Gläsker S, Bender BU, Apel TW, Natt E, van Velthoven V, Scheremet R, Zentner J, Neumann HP.

J Neurol Neurosurg Psychiatry. 1999 Dec;67(6):758-62.

PubMed [citation]
PMID:
10567493
PMCID:
PMC1736691
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000959261.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the VHL protein in which other variant(s) (p.Ser183*) have been determined to be pathogenic (PMID: 8707293, 10567493, 11309459). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 93329). This variant is also known as "8-nt insertion (714)" or "715 insTTGTCCGT". This premature translational stop signal has been observed in individual(s) with von Hippel-Lindau syndrome (PMID: 7728151, 8493574). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser168Leufs*5) in the VHL gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 46 amino acid(s) of the VHL protein.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024