NM_000551.4(VHL):c.548C>T (p.Ser183Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 27, 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:: RCV002349982.10

Allele description [Variation Report for NM_000551.4(VHL):c.548C>T (p.Ser183Leu)]

NM_000551.4(VHL):c.548C>T (p.Ser183Leu)

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.548C>T (p.Ser183Leu)

HGVS:

NC_000003.12:g.10149871C>T
NG_008212.3:g.13237C>T
NG_046756.1:g.7633C>T
NM_000551.4:c.548C>TMANE SELECT
NM_001354723.2:c.*102C>T
NM_198156.3:c.425C>T
NP_000542.1:p.Ser183Leu
NP_000542.1:p.Ser183Leu
NP_937799.1:p.Ser142Leu
LRG_322t1:c.548C>T
LRG_322:g.13237C>T
LRG_322p1:p.Ser183Leu
NC_000003.11:g.10191555C>T
NM_000551.3:c.548C>T

Protein change:

S142L; SER183LEU

Links:

OMIM: 608537.0029; dbSNP: rs5030823

NCBI 1000 Genomes Browser:

rs5030823

Molecular consequence:

NM_001354723.2:c.*102C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000551.4:c.548C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.425C>T - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002648267	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 27, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002648267

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 27, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Prevalence of Germline Variants in a Large Cohort of Japanese Patients with Pheochromocytoma and/or Paraganglioma.

Yonamine M, Wasano K, Aita Y, Sugasawa T, Takahashi K, Kawakami Y, Shimano H, Nishiyama H, Hara H, Naruse M, Okamoto T, Matsuda T, Kosugi S, Horiguchi K, Tanabe A, Watanabe A, Kimura N, Nakamura E, Sakurai A, Shiga K, Takekoshi K.

Cancers (Basel). 2021 Aug 9;13(16). doi:pii: 4014. 10.3390/cancers13164014.

PubMed [citation]

PMID:: 34439168
PMCID:: PMC8394264

Details of each submission

From Ambry Genetics, SCV002648267.3

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

Description

The p.S183L variant (also known as c.548C>T), located in coding exon 3 of the VHL gene, results from a C to T substitution at nucleotide position 548. The serine at codon 183 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been reported in an individual with a paraganglioma diagnosed at age 28 (Crona J et al. PLoS ONE 2014 Jan;9(1):e86756) and also in a compound heterozygous state (with VHL p.D126N) in an individual with hereditary erythrocytosis (Bond J et al. Blood 2011 Mar;117(13):3699-701). This variant was also detected in 1/370 Japanese pheochromocytoma/paraganglioma (PPGL) patients and classified as a variant of uncertain significance by the authors (Yonamine M et al. Cancers (Basel), 2021 Aug;13). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Aug 18, 2024

ClinVar

Relating variation to medicine