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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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002648267Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Mar 27, 2023) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

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

Last Updated: Oct 26, 2024