NM_000551.4(VHL):c.501_502insTTGTCCGT (p.Ser168fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 20, 2021
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:: RCV001023415.3

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:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001185285	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 20, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 7728151, 8493574 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001185285

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 20, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Citations

PubMed

Germline mutations in the von Hippel-Lindau disease tumor suppressor gene: correlations with phenotype.

Chen F, Kishida T, Yao M, Hustad T, Glavac D, Dean M, Gnarra JR, Orcutt ML, Duh FM, Glenn G, et al.

Hum Mutat. 1995;5(1):66-75.

PubMed [citation]

PMID:: 7728151

Identification of the von Hippel-Lindau disease tumor suppressor gene.

Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L, et al.

Science. 1993 May 28;260(5112):1317-20.

PubMed [citation]

PMID:: 8493574

Details of each submission

From Ambry Genetics, SCV001185285.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The c.501_502insTTGTCCGT pathogenic mutation, located in coding exon 3 of the VHL gene, results from an insertion of 8 nucleotides at position 501, causing a translational frameshift with a predicted alternate stop codon (p.S168Lfs*5). This alteration has been identified in Von Hippel-Lindau families (Latif F et al. Science, 1993 May;260:1317-20; Chen F et al. Hum. Mutat., 1995;5:66-75). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.

#	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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